SPI1

UniProt ID: P17947
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

SPI1 encodes PU.1, an ETS-family pioneer transcription factor expressed mainly in hematopoietic and immune lineages. PU.1 localizes to nucleus, nucleoplasm, chromatin, and transcription-regulator complexes, where its ETS domain binds purine-rich PU-box/cis-regulatory DNA motifs and works with other transcription factors and chromatin cofactors to activate or repress RNA polymerase II transcription. By opening or selecting regulatory chromatin and coordinating lineage-specific transcriptional programs, PU.1 controls myeloid, macrophage/microglial, dendritic-cell, B-cell, and broader hematopoietic differentiation and immune-cell functional states.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
IBA
GO_REF:0000033 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0030154 cell differentiation
IBA
GO_REF:0000033 		ACCEPT
Summary: PU.1 regulates hematopoietic lineage fate, especially myeloid/macrophage, dendritic-cell, and B-cell development.
Reason: Retain as core or near-core developmental biology because PU.1 deficiency or mutation disrupts lymphoid and myeloid development, while iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, PMID:33951726).
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IBA
GO_REF:0000033 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0006357 regulation of transcription by RNA polymerase II
IBA
GO_REF:0000033 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000120 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0006357 regulation of transcription by RNA polymerase II
IEA
GO_REF:0000002 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0043565 sequence-specific DNA binding
IEA
GO_REF:0000120 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0005515 protein binding
IPI
PMID:18250304
Gain-of-function mutation of GATA-2 in acute myeloid transfo... 		MODIFY
Summary: The cited interaction reflects PU.1 cooperation with transcription factors or transcriptional cofactors rather than generic protein binding.
Reason: Modify generic protein binding to transcription-factor/cofactor binding where the evidence supports PU.1 physical or functional interaction with another transcriptional regulator.
GO:0005515 protein binding
IPI
PMID:18692240
Physical and functional interactions between hematopoietic c... 		MODIFY
Summary: The cited interaction reflects PU.1 cooperation with transcription factors or transcriptional cofactors rather than generic protein binding.
Reason: Modify generic protein binding to transcription-factor/cofactor binding where the evidence supports PU.1 physical or functional interaction with another transcriptional regulator.
GO:0005515 protein binding
IPI
PMID:20159610
PML/RARalpha targets promoter regions containing PU.1 consen... 		MODIFY
Summary: The cited interaction reflects PU.1 cooperation with transcription factors or transcriptional cofactors rather than generic protein binding.
Reason: Modify generic protein binding to transcription-factor/cofactor binding where the evidence supports PU.1 physical or functional interaction with another transcriptional regulator.
GO:0005515 protein binding
IPI
PMID:21575865
Mechanistic rationale for inhibition of poly(ADP-ribose) pol... 		UNDECIDED
Summary: The cached abstract is abstract-only or focused on another ETS/fusion context and does not expose enough evidence to verify the SPI1-specific interaction.
Reason: Use UNDECIDED rather than removing the experimental annotation because the curator may have used full-text evidence not present in the cache; the abstract alone does not establish this SPI1-specific generic protein-binding assertion.
GO:0000122 negative regulation of transcription by RNA polymerase II
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000785 chromatin
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000987 cis-regulatory region sequence-specific DNA binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0002314 germinal center B cell differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0002316 follicular B cell differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0002327 immature B cell differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0002572 pro-T cell differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0003677 DNA binding
IEA
GO_REF:0000107 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0003682 chromatin binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription factor that selects accessible and inaccessible binding sites and shapes hematopoietic chromatin accessibility.
Reason: Retain as core because PU.1 occupies active chromatin domains, can bind high-affinity sites in DNase-inaccessible regions, and controls hematopoietic euchromatin accessibility and transcription-factor access (PMID:23658224, PMID:33951726).
GO:0007179 transforming growth factor beta receptor signaling pathway
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0010628 positive regulation of gene expression
IEA
GO_REF:0000107 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0010629 negative regulation of gene expression
IEA
GO_REF:0000107 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0030316 osteoclast differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0031663 lipopolysaccharide-mediated signaling pathway
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0042826 histone deacetylase binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0043314 negative regulation of neutrophil degranulation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0045347 negative regulation of MHC class II biosynthetic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0045471 response to ethanol
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0045815 transcription initiation-coupled chromatin remodeling
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription factor that selects accessible and inaccessible binding sites and shapes hematopoietic chromatin accessibility.
Reason: Retain as core because PU.1 occupies active chromatin domains, can bind high-affinity sites in DNase-inaccessible regions, and controls hematopoietic euchromatin accessibility and transcription-factor access (PMID:23658224, PMID:33951726).
GO:0045892 negative regulation of DNA-templated transcription
IEA
GO_REF:0000120 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045893 positive regulation of DNA-templated transcription
IEA
GO_REF:0000107 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0051525 NFAT protein binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0071361 cellular response to ethanol
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0090402 oncogene-induced cell senescence
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0098508 endothelial to hematopoietic transition
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0120186 negative regulation of protein localization to chromatin
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0140297 DNA-binding transcription factor binding
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0140311 protein sequestering activity
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:1900745 positive regulation of p38MAPK cascade
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1902895 positive regulation of miRNA transcription
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1904151 positive regulation of microglial cell mediated cytotoxicity
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1904178 negative regulation of adipose tissue development
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:1904238 pericyte cell differentiation
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:1905036 positive regulation of antifungal innate immune response
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1905453 regulation of myeloid progenitor cell differentiation
IEA
GO_REF:0000107 		ACCEPT
Summary: PU.1 regulates hematopoietic lineage fate, especially myeloid/macrophage, dendritic-cell, and B-cell development.
Reason: Retain as core or near-core developmental biology because PU.1 deficiency or mutation disrupts lymphoid and myeloid development, while iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, PMID:33951726).
GO:2000529 positive regulation of myeloid dendritic cell chemotaxis
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0043124 negative regulation of canonical NF-kappaB signal transduction
IDA
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0045815 transcription initiation-coupled chromatin remodeling
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription factor that selects accessible and inaccessible binding sites and shapes hematopoietic chromatin accessibility.
Reason: Retain as core because PU.1 occupies active chromatin domains, can bind high-affinity sites in DNase-inaccessible regions, and controls hematopoietic euchromatin accessibility and transcription-factor access (PMID:23658224, PMID:33951726).
GO:0005515 protein binding
IPI
PMID:33951726
Constrained chromatin accessibility in PU.1-mutated agammagl... 		MODIFY
Summary: The cited interaction reflects PU.1 cooperation with transcription factors or transcriptional cofactors rather than generic protein binding.
Reason: Modify generic protein binding to transcription-factor/cofactor binding where the evidence supports PU.1 physical or functional interaction with another transcriptional regulator.
GO:0005634 nucleus
IDA
PMID:33951726
Constrained chromatin accessibility in PU.1-mutated agammagl... 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0043565 sequence-specific DNA binding
IDA
PMID:33951726
Constrained chromatin accessibility in PU.1-mutated agammagl... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0045579 positive regulation of B cell differentiation
IMP
PMID:33951726
Constrained chromatin accessibility in PU.1-mutated agammagl... 		ACCEPT
Summary: PU.1 regulates hematopoietic lineage fate, especially myeloid/macrophage, dendritic-cell, and B-cell development.
Reason: Retain as core or near-core developmental biology because PU.1 deficiency or mutation disrupts lymphoid and myeloid development, while iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, PMID:33951726).
GO:0045815 transcription initiation-coupled chromatin remodeling
IMP
PMID:33951726
Constrained chromatin accessibility in PU.1-mutated agammagl... 		ACCEPT
Summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription factor that selects accessible and inaccessible binding sites and shapes hematopoietic chromatin accessibility.
Reason: Retain as core because PU.1 occupies active chromatin domains, can bind high-affinity sites in DNase-inaccessible regions, and controls hematopoietic euchromatin accessibility and transcription-factor access (PMID:23658224, PMID:33951726).
GO:0002357 defense response to tumor cell
IMP
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0036462 TRAIL-activated apoptotic signaling pathway
IMP
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IPI
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0097677 STAT family protein binding
IPI
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0000987 cis-regulatory region sequence-specific DNA binding
IDA
PMID:28481873
Restoring PU.1 induces apoptosis and modulates viral transac... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0002357 defense response to tumor cell
IMP
PMID:28481873
Restoring PU.1 induces apoptosis and modulates viral transac... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:28481873
Restoring PU.1 induces apoptosis and modulates viral transac... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000122 negative regulation of transcription by RNA polymerase II
IMP
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:12833137
CDK6 blocks differentiation: coupling cell proliferation to ... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:20139074
Metallothionein-1 isoforms and vimentin are direct PU.1 down... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:27506447
Transcriptional regulation of the proto-oncogene Zfp521 by S... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:27506447
Transcriptional regulation of the proto-oncogene Zfp521 by S... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:30718772
A transcription factor PU.1 is critical for Ccl22 gene expre... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:31146003
Androgen upregulates NR4A1 via the TFAP2A and ETS signaling ... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:31314592
PU.1 plays a pivotal role in dendritic cell migration from t... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:1902895 positive regulation of miRNA transcription
IDA
PMID:20972335
Hypoxia-induced microRNA-424 expression in human endothelial... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0001216 DNA-binding transcription activator activity
IDA
PMID:20139074
Metallothionein-1 isoforms and vimentin are direct PU.1 down... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0001217 DNA-binding transcription repressor activity
IDA
PMID:20139074
Metallothionein-1 isoforms and vimentin are direct PU.1 down... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0098508 endothelial to hematopoietic transition
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1905453 regulation of myeloid progenitor cell differentiation
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 regulates hematopoietic lineage fate, especially myeloid/macrophage, dendritic-cell, and B-cell development.
Reason: Retain as core or near-core developmental biology because PU.1 deficiency or mutation disrupts lymphoid and myeloid development, while iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, PMID:33951726).
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IPI
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:1901223 negative regulation of non-canonical NF-kappaB signal transduction
IMP
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-m... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1904178 negative regulation of adipose tissue development
ISS
GO_REF:0000024 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0000987 cis-regulatory region sequence-specific DNA binding
IDA
PMID:30718772
A transcription factor PU.1 is critical for Ccl22 gene expre... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000987 cis-regulatory region sequence-specific DNA binding
IDA
PMID:31314592
PU.1 plays a pivotal role in dendritic cell migration from t... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:1904238 pericyte cell differentiation
ISS
GO_REF:0000024 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0000976 transcription cis-regulatory region binding
IDA
PMID:31146003
Androgen upregulates NR4A1 via the TFAP2A and ETS signaling ... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000976 transcription cis-regulatory region binding
IMP
PMID:27506447
Transcriptional regulation of the proto-oncogene Zfp521 by S... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:27506447
Transcriptional regulation of the proto-oncogene Zfp521 by S... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0140297 DNA-binding transcription factor binding
IPI
PMID:27506447
Transcriptional regulation of the proto-oncogene Zfp521 by S... 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0002357 defense response to tumor cell
IMP
PMID:30429596
In vitro conversion of adult murine endothelial cells to hem... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0005634 nucleus
IDA
PMID:24504023
Dual regulation of SPI1/PU.1 transcription factor by heat sh... 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000987 cis-regulatory region sequence-specific DNA binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0002572 pro-T cell differentiation
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0003682 chromatin binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription factor that selects accessible and inaccessible binding sites and shapes hematopoietic chromatin accessibility.
Reason: Retain as core because PU.1 occupies active chromatin domains, can bind high-affinity sites in DNase-inaccessible regions, and controls hematopoietic euchromatin accessibility and transcription-factor access (PMID:23658224, PMID:33951726).
GO:0003700 DNA-binding transcription factor activity
ISS
GO_REF:0000024 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0002573 myeloid leukocyte differentiation
IMP
PMID:28111278
Human Induced Pluripotent Stem Cell-Derived Macrophages Shar... 		ACCEPT
Summary: PU.1 regulates hematopoietic lineage fate, especially myeloid/macrophage, dendritic-cell, and B-cell development.
Reason: Retain as core or near-core developmental biology because PU.1 deficiency or mutation disrupts lymphoid and myeloid development, while iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, PMID:33951726).
GO:1904151 positive regulation of microglial cell mediated cytotoxicity
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0000987 cis-regulatory region sequence-specific DNA binding
IDA
PMID:31018969
A Recurrent Activating Missense Mutation in WaldenstrΓΆm Macr... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:31018969
A Recurrent Activating Missense Mutation in WaldenstrΓΆm Macr... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0006355 regulation of DNA-templated transcription
IDA
PMID:31018969
A Recurrent Activating Missense Mutation in WaldenstrΓΆm Macr... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0045892 negative regulation of DNA-templated transcription
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0140297 DNA-binding transcription factor binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0140311 protein sequestering activity
ISS
GO_REF:0000024 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:0000122 negative regulation of transcription by RNA polymerase II
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0042826 histone deacetylase binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0043314 negative regulation of neutrophil degranulation
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0120186 negative regulation of protein localization to chromatin
ISS
GO_REF:0000024 		MARK AS OVER ANNOTATED
Summary: This annotation is a narrow disease, cell-line, high-throughput, or non-core downstream context and does not define SPI1/PU.1 core function.
Reason: Mark as over-annotated because the reviewed evidence supports PU.1 as a hematopoietic ETS transcription factor, while this term is peripheral, context-specific, or too downstream for core function curation.
GO:1905036 positive regulation of antifungal innate immune response
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0010629 negative regulation of gene expression
IMP
PMID:29290617
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiati... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0090402 oncogene-induced cell senescence
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:1900745 positive regulation of p38MAPK cascade
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0000785 chromatin
ISA
GO_REF:0000113 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
ISA
GO_REF:0000113 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0005667 transcription regulator complex
IDA
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0070102 interleukin-6-mediated signaling pathway
IDA
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IDA
PMID:20139074
Metallothionein-1 isoforms and vimentin are direct PU.1 down... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0005634 nucleus
IDA
PMID:20972335
Hypoxia-induced microRNA-424 expression in human endothelial... 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0005515 protein binding
IPI
PMID:26019275
A Novel In-Frame Deletion in the Leucine Zipper Domain of C/... 		MODIFY
Summary: The cited interaction reflects PU.1 cooperation with transcription factors or transcriptional cofactors rather than generic protein binding.
Reason: Modify generic protein binding to transcription-factor/cofactor binding where the evidence supports PU.1 physical or functional interaction with another transcriptional regulator.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9617064 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9617207 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:1902895 positive regulation of miRNA transcription
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0051525 NFAT protein binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
ISS
GO_REF:0000024 		ACCEPT
Summary: PU.1 physically or functionally cooperates with transcription factors and chromatin/transcriptional cofactors.
Reason: Retain because PU.1 function includes cooperative binding with other transcriptional regulators and cofactors at hematopoietic regulatory elements (PMID:23658224, PMID:33951726).
GO:0000785 chromatin
IDA
PMID:15304486
Essential role of p38 mitogen-activated protein kinase in ca... 		ACCEPT
Summary: PU.1 is a nuclear/chromatin transcription factor.
Reason: Retain because PU.1 functions in the nucleus, nucleoplasm, chromatin, and transcription-regulator complexes to bind regulatory DNA and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0045892 negative regulation of DNA-templated transcription
IDA
PMID:20139074
Metallothionein-1 isoforms and vimentin are direct PU.1 down... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:12833137
CDK6 blocks differentiation: coupling cell proliferation to ... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0045646 regulation of erythrocyte differentiation
IMP
PMID:12833137
CDK6 blocks differentiation: coupling cell proliferation to ... 		KEEP AS NON CORE
Summary: This lineage or immune-cell phenotype is compatible with PU.1 biology but is downstream or cell-type-specific.
Reason: Keep as non-core because it reflects a particular hematopoietic, immune, inflammatory, or disease-context outcome of PU.1 transcriptional control rather than the defining DNA-binding/chromatin-regulatory molecular function.
GO:0005515 protein binding
IPI
PMID:10207087
Functional and physical interactions between AML1 proteins a... 		UNDECIDED
Summary: The cached abstract is abstract-only or focused on another ETS/fusion context and does not expose enough evidence to verify the SPI1-specific interaction.
Reason: Use UNDECIDED rather than removing the experimental annotation because the curator may have used full-text evidence not present in the cache; the abstract alone does not establish this SPI1-specific generic protein-binding assertion.
GO:0000122 negative regulation of transcription by RNA polymerase II
TAS
PMID:10867017
The hematopoietic transcription factor PU.1 represses gelati... 		ACCEPT
Summary: PU.1/SPI1 is an ETS-domain transcription factor that binds PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase II transcription.
Reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS motif, binds cis-regulatory regions in vivo, and controls hematopoietic gene expression as a DNA-binding transcription factor (PMID:2180582, PMID:23658224, PMID:33951726).
GO:0003700 DNA-binding transcription factor activity
TAS
PMID:10867017
The hematopoietic transcription factor PU.1 represses gelati... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.
GO:0003700 DNA-binding transcription factor activity
TAS
PMID:2180582
The macrophage and B cell-specific transcription factor PU.1... 		MODIFY
Summary: The annotation is directionally correct but too broad for PU.1; the specific biology is RNA polymerase II cis-regulatory DNA binding and transcription factor activity.
Reason: Modify to a more informative PU.1 transcription-factor term because generic DNA binding or DNA-templated transcription regulation obscures the ETS-domain cis-regulatory/RNA polymerase II mechanism.

Core Functions

ETS-domain cis-regulatory DNA binding and RNA polymerase II transcription-factor activity at PU-box/ETS motifs in hematopoietic regulatory elements.

Molecular Function:
DNA-binding transcription factor activity, RNA polymerase II-specific
Directly Involved In:
regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II
Cellular Locations:
nucleus nucleoplasm chromatin
Supporting Evidence:
  • PMID:2180582
    the PU.1 protein recognized a purine-rich sequence, 5'-GAGGAA-3' (PU box)
  • PMID:2180582
    The PU.1 protein was shown to be a transcriptional activator that is expressed in macrophages and B cells
  • PMID:23658224
    PU.1 selects its binding sites primarily based on sequence affinity

Pioneer/chromatin-regulatory activity that opens or selects hematopoietic regulatory chromatin and permits cooperative transcription-factor access.

Molecular Function:
chromatin binding
Directly Involved In:
transcription initiation-coupled chromatin remodeling cell differentiation
Cellular Locations:
chromatin nucleus
Supporting Evidence:
  • PMID:23658224
    Occupied sites were predominantly detected in active chromatin domains
  • PMID:33951726
    decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter
  • PMID:33951726
    destabilized PU.1 proteins unable to nuclear localize or bind target DNA

Hematopoietic lineage specification and differentiation, especially B-cell, myeloid/macrophage, dendritic-cell, and microglia-related macrophage programs, through PU.1-dependent transcriptional control.

Molecular Function:
DNA-binding transcription factor activity, RNA polymerase II-specific
Directly Involved In:
myeloid leukocyte differentiation positive regulation of B cell differentiation regulation of myeloid progenitor cell differentiation
Cellular Locations:
nucleus chromatin
Supporting Evidence:
  • PMID:33951726
    Affected patients lacked circulating B cells and possessed few conventional dendritic cells
  • PMID:33951726
    mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation
  • PMID:28111278
    human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1)-dependent fashion

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000113
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10207087
Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias.
PMID:10867017
The hematopoietic transcription factor PU.1 represses gelatinase A transcription in glomerular mesangial cells.
PMID:12833137
CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells.
PMID:15304486
Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1.
PMID:18250304
Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia.
PMID:18692240
Physical and functional interactions between hematopoietic cell-specific ETS transcription factors and homeodomain proteins.
PMID:20139074
Metallothionein-1 isoforms and vimentin are direct PU.1 downstream target genes in leukemia cells.
PMID:20159610
PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia.
PMID:20972335
Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-Ξ± isoforms and promotes angiogenesis.
PMID:21575865
Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer.
PMID:2180582
The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene.
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.
PMID:24504023
Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes.
PMID:26019275
A Novel In-Frame Deletion in the Leucine Zipper Domain of C/EBPΞ΅ Leads to Neutrophil-Specific Granule Deficiency.
PMID:27506447
Transcriptional regulation of the proto-oncogene Zfp521 by SPI1 (PU.1) and HOXC13.
PMID:28111278
Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages.
PMID:28362429
PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-mediated cell survival and inducing DR5 expression.
PMID:28481873
Restoring PU.1 induces apoptosis and modulates viral transactivation via interferon-stimulated genes in primary effusion lymphoma.
PMID:29290617
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m(6)A Modification.
PMID:30429596
In vitro conversion of adult murine endothelial cells to hematopoietic stem cells.
PMID:30718772
A transcription factor PU.1 is critical for Ccl22 gene expression in dendritic cells and macrophages.
PMID:31018969
A Recurrent Activating Missense Mutation in WaldenstrΓΆm Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor SPI1 and Enhances Proliferation.
PMID:31146003
Androgen upregulates NR4A1 via the TFAP2A and ETS signaling networks.
PMID:31314592
PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs via regulating CCR7 expression.
PMID:33951726
Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.
Reactome:R-HSA-9617064
SPI1 (PU.1), PML isoform 4, and EP300 bind the promoter of the CEBPE gene
Reactome:R-HSA-9617207
SPI1 (PU.1), CEBPA and DEK bind the promoter of the CSF3R (G-CSFR) gene
PMID:23658224
Mechanisms of in vivo binding site selection of the hematopoietic master transcription factor PU.1.

Suggested Questions for Experts

Q: Which SPI1-dependent microglial terms should be curated as direct lineage-maintenance functions rather than downstream immune-cell outcomes?

Q: Can full-text evidence for the abstract-only ETS-family interaction annotations be reviewed to decide whether SPI1-specific protein-binding assertions should be accepted or removed?

Suggested Experiments

Experiment: Perform matched PU.1 ChIP-seq/CUT&RUN and ATAC-seq in primary or iPSC-derived human microglia carrying relevant SPI1 regulatory haplotypes.

Hypothesis: Alzheimer-associated SPI1 regulatory variation alters PU.1 occupancy and chromatin accessibility in microglia.

Type: microglial chromatin profiling

Experiment: Compare SPI1 titration or degron perturbation across human B-cell precursors and microglia-like cells with RNA-seq and chromatin accessibility readouts.

Hypothesis: PU.1 dosage controls distinct B-cell and microglial target-gene programs through shared ETS motif occupancy but different cooperative factors.

Type: dose-response perturbation genomics

πŸ“š Additional Documentation

Notes

(SPI1-notes.md)

SPI1 notes

Automated deep research was attempted with just deep-research-falcon human SPI1 --fallback perplexity-lite, but the run timed out before producing a deep-research file. This review therefore uses the cached GOA publications, UniProt record, Reactome-derived entries, and PANTHER family fetch.

SPI1 encodes PU.1, an ETS-family transcription factor expressed in hematopoietic and immune lineages. The original PU.1 cloning paper describes it as a tissue-specific DNA-binding transcription factor: PU.1 recognized the purine-rich PU-box motif 5'-GAGGAA-3' and acted as a transcriptional activator expressed in macrophages and B cells [PMID:2180582 "the PU.1 protein recognized a purine-rich sequence, 5'-GAGGAA-3' (PU box)"; PMID:2180582 "The PU.1 protein was shown to be a transcriptional activator that is expressed in macrophages and B cells"].

The core molecular function is ETS-domain sequence-specific cis-regulatory DNA binding coupled to transcriptional activation or repression by RNA polymerase II. In human macrophage differentiation, PU.1 binding-site selection depends on sequence affinity, PU.1 concentration, cooperative transcription-factor interactions, and chromatin accessibility [PMID:23658224 "PU.1 selects its binding sites primarily based on sequence affinity"; PMID:23658224 "PU.1 binding control that involves motif-binding affinity, PU.1 concentration, cooperativeness with neighboring transcription factor sites and chromatin domain accessibility"]. PU.1 occupied sites are enriched in active chromatin domains with nearby cooperative motifs PMID:23658224.

PU.1 has pioneer/master-regulator biology in hematopoiesis. A human immunodeficiency study states that PU.1 controls hematopoietic cell fate by decompacting stem-cell heterochromatin and opening otherwise inaccessible genomic sites PMID:33951726. Patient and genome-editing evidence showed SPI1-dependent B-cell, dendritic-cell, and myeloid development: affected patients lacked B cells and had few conventional dendritic cells, disease-similar SPI1 mutations impaired early B-cell and myeloid differentiation, and mutant proteins failed to nuclear-localize or bind target DNA [PMID:33951726 "Affected patients lacked circulating B cells and possessed few conventional dendritic cells"; PMID:33951726 "mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation"; PMID:33951726 "Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA"].

SPI1 is relevant to microglia/macrophage biology through its lineage role rather than a narrow Alzheimer-specific effector mechanism. Human iPSC-derived monocyte/macrophage experiments showed SPI1 dependence and related those cells to tissue-resident macrophages including microglia [PMID:28111278 "human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1)-dependent fashion"; PMID:28111278 "a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells"]. This supports retaining myeloid/macrophage lineage annotations as important but generally non-core relative to the defining transcription-factor and chromatin-regulatory function.

For curation, keep DNA-binding transcription-factor activity, cis-regulatory region binding, chromatin binding, nuclear/chromatin/nucleoplasm localization, RNA polymerase II transcription regulation, and transcription initiation-coupled chromatin remodeling as core. Keep hematopoietic lineage outcomes, macrophage/myeloid differentiation, B-cell differentiation, endothelial-to-hematopoietic transition, dendritic-cell chemotaxis, and microglial/immune effector terms as non-core developmental or cell-type outcomes unless they directly describe PU.1's transcriptional control mechanism. Generic protein binding should be modified to specific transcription-factor binding, STAT-family protein binding, histone deacetylase binding, NFAT binding, or marked over-annotated when the original evidence is a generic interaction screen.

2026-06-20 second-pass audit

The second-pass audit left the two remaining generic protein binding IPI annotations as UNDECIDED rather than removing them. PMID:21575865 is cached as abstract-only and foregrounds TMPRSS2:ERG interaction with PARP1/DNA-PKcs in ETS fusion-positive prostate cancer, not a directly visible SPI1 assay PMID:21575865. PMID:10207087 is likewise abstract-only in the cache and describes MEF/AML1 interactions, not an exposed SPI1 interaction PMID:10207087. Under the project rule not to overrule experimental annotations from incomplete abstract-only evidence, both calls should remain unresolved pending full-text or supplementary-data review.

πŸ“„ View Raw YAML

 
id: P17947
gene_symbol: SPI1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'SPI1 encodes PU.1, an ETS-family pioneer transcription factor expressed
  mainly in hematopoietic and immune lineages. PU.1 localizes to nucleus, nucleoplasm,
  chromatin, and transcription-regulator complexes, where its ETS domain binds purine-rich
  PU-box/cis-regulatory DNA motifs and works with other transcription factors and
  chromatin cofactors to activate or repress RNA polymerase II transcription. By opening
  or selecting regulatory chromatin and coordinating lineage-specific transcriptional
  programs, PU.1 controls myeloid, macrophage/microglial, dendritic-cell, B-cell,
  and broader hematopoietic differentiation and immune-cell functional states.'
alternative_products:
- name: '1'
  id: P17947-1
- name: '2'
  id: P17947-2
  sequence_note: VSP_038690
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: PU.1 regulates hematopoietic lineage fate, especially 
      myeloid/macrophage, dendritic-cell, and B-cell development.
    action: ACCEPT
    reason: Retain as core or near-core developmental biology because PU.1 
      deficiency or mutation disrupts lymphoid and myeloid development, while 
      iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, 
      PMID:33951726).
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0006357
      label: regulation of transcription by RNA polymerase II
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000987
      label: cis-regulatory region sequence-specific DNA binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18250304
  qualifier: enables
  review:
    summary: The cited interaction reflects PU.1 cooperation with transcription 
      factors or transcriptional cofactors rather than generic protein binding.
    action: MODIFY
    reason: Modify generic protein binding to transcription-factor/cofactor 
      binding where the evidence supports PU.1 physical or functional 
      interaction with another transcriptional regulator.
    proposed_replacement_terms:
    - id: GO:0140297
      label: DNA-binding transcription factor binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18692240
  qualifier: enables
  review:
    summary: The cited interaction reflects PU.1 cooperation with transcription 
      factors or transcriptional cofactors rather than generic protein binding.
    action: MODIFY
    reason: Modify generic protein binding to transcription-factor/cofactor 
      binding where the evidence supports PU.1 physical or functional 
      interaction with another transcriptional regulator.
    proposed_replacement_terms:
    - id: GO:0140297
      label: DNA-binding transcription factor binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20159610
  qualifier: enables
  review:
    summary: The cited interaction reflects PU.1 cooperation with transcription 
      factors or transcriptional cofactors rather than generic protein binding.
    action: MODIFY
    reason: Modify generic protein binding to transcription-factor/cofactor 
      binding where the evidence supports PU.1 physical or functional 
      interaction with another transcriptional regulator.
    proposed_replacement_terms:
    - id: GO:0140297
      label: DNA-binding transcription factor binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21575865
  qualifier: enables
  review:
    summary: The cached abstract is abstract-only or focused on another 
      ETS/fusion context and does not expose enough evidence to verify the 
      SPI1-specific interaction.
    action: UNDECIDED
    reason: Use UNDECIDED rather than removing the experimental annotation 
      because the curator may have used full-text evidence not present in the 
      cache; the abstract alone does not establish this SPI1-specific generic 
      protein-binding assertion.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0001227
    label: DNA-binding transcription repressor activity, RNA polymerase 
      II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0001228
    label: DNA-binding transcription activator activity, RNA polymerase 
      II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0002314
    label: germinal center B cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0002316
    label: follicular B cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0002327
    label: immature B cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0002572
    label: pro-T cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000987
      label: cis-regulatory region sequence-specific DNA binding
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription 
      factor that selects accessible and inaccessible binding sites and shapes 
      hematopoietic chromatin accessibility.
    action: ACCEPT
    reason: Retain as core because PU.1 occupies active chromatin domains, can 
      bind high-affinity sites in DNase-inaccessible regions, and controls 
      hematopoietic euchromatin accessibility and transcription-factor access 
      (PMID:23658224, PMID:33951726).
- term:
    id: GO:0007179
    label: transforming growth factor beta receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
- term:
    id: GO:0030316
    label: osteoclast differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0031663
    label: lipopolysaccharide-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0042826
    label: histone deacetylase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0043314
    label: negative regulation of neutrophil degranulation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0045347
    label: negative regulation of MHC class II biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0045815
    label: transcription initiation-coupled chromatin remodeling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription 
      factor that selects accessible and inaccessible binding sites and shapes 
      hematopoietic chromatin accessibility.
    action: ACCEPT
    reason: Retain as core because PU.1 occupies active chromatin domains, can 
      bind high-affinity sites in DNase-inaccessible regions, and controls 
      hematopoietic euchromatin accessibility and transcription-factor access 
      (PMID:23658224, PMID:33951726).
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0051525
    label: NFAT protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0071361
    label: cellular response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0090402
    label: oncogene-induced cell senescence
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0098508
    label: endothelial to hematopoietic transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0120186
    label: negative regulation of protein localization to chromatin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0140311
    label: protein sequestering activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:1900745
    label: positive regulation of p38MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1904151
    label: positive regulation of microglial cell mediated cytotoxicity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1904178
    label: negative regulation of adipose tissue development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:1904238
    label: pericyte cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:1905036
    label: positive regulation of antifungal innate immune response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1905453
    label: regulation of myeloid progenitor cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: PU.1 regulates hematopoietic lineage fate, especially 
      myeloid/macrophage, dendritic-cell, and B-cell development.
    action: ACCEPT
    reason: Retain as core or near-core developmental biology because PU.1 
      deficiency or mutation disrupts lymphoid and myeloid development, while 
      iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, 
      PMID:33951726).
- term:
    id: GO:2000529
    label: positive regulation of myeloid dendritic cell chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: IDA
  original_reference_id: PMID:28362429
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0045815
    label: transcription initiation-coupled chromatin remodeling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription 
      factor that selects accessible and inaccessible binding sites and shapes 
      hematopoietic chromatin accessibility.
    action: ACCEPT
    reason: Retain as core because PU.1 occupies active chromatin domains, can 
      bind high-affinity sites in DNase-inaccessible regions, and controls 
      hematopoietic euchromatin accessibility and transcription-factor access 
      (PMID:23658224, PMID:33951726).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33951726
  qualifier: enables
  review:
    summary: The cited interaction reflects PU.1 cooperation with transcription 
      factors or transcriptional cofactors rather than generic protein binding.
    action: MODIFY
    reason: Modify generic protein binding to transcription-factor/cofactor 
      binding where the evidence supports PU.1 physical or functional 
      interaction with another transcriptional regulator.
    proposed_replacement_terms:
    - id: GO:0140297
      label: DNA-binding transcription factor binding
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:33951726
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:33951726
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000987
      label: cis-regulatory region sequence-specific DNA binding
- term:
    id: GO:0045579
    label: positive regulation of B cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:33951726
  qualifier: involved_in
  review:
    summary: PU.1 regulates hematopoietic lineage fate, especially 
      myeloid/macrophage, dendritic-cell, and B-cell development.
    action: ACCEPT
    reason: Retain as core or near-core developmental biology because PU.1 
      deficiency or mutation disrupts lymphoid and myeloid development, while 
      iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, 
      PMID:33951726).
- term:
    id: GO:0045815
    label: transcription initiation-coupled chromatin remodeling
  evidence_type: IMP
  original_reference_id: PMID:33951726
  qualifier: involved_in
  review:
    summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription 
      factor that selects accessible and inaccessible binding sites and shapes 
      hematopoietic chromatin accessibility.
    action: ACCEPT
    reason: Retain as core because PU.1 occupies active chromatin domains, can 
      bind high-affinity sites in DNase-inaccessible regions, and controls 
      hematopoietic euchromatin accessibility and transcription-factor access 
      (PMID:23658224, PMID:33951726).
- term:
    id: GO:0002357
    label: defense response to tumor cell
  evidence_type: IMP
  original_reference_id: PMID:28362429
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0036462
    label: TRAIL-activated apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:28362429
  qualifier: acts_upstream_of_positive_effect
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:24429361
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0097677
    label: STAT family protein binding
  evidence_type: IPI
  original_reference_id: PMID:24429361
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:28481873
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0002357
    label: defense response to tumor cell
  evidence_type: IMP
  original_reference_id: PMID:28481873
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:28481873
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:28362429
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:12833137
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:20139074
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:27506447
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:27506447
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:28362429
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:30718772
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:31146003
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:31314592
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: IDA
  original_reference_id: PMID:20972335
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0001216
    label: DNA-binding transcription activator activity
  evidence_type: IDA
  original_reference_id: PMID:20139074
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0001217
    label: DNA-binding transcription repressor activity
  evidence_type: IDA
  original_reference_id: PMID:20139074
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0098508
    label: endothelial to hematopoietic transition
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1905453
    label: regulation of myeloid progenitor cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: PU.1 regulates hematopoietic lineage fate, especially 
      myeloid/macrophage, dendritic-cell, and B-cell development.
    action: ACCEPT
    reason: Retain as core or near-core developmental biology because PU.1 
      deficiency or mutation disrupts lymphoid and myeloid development, while 
      iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, 
      PMID:33951726).
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:28362429
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:1901223
    label: negative regulation of non-canonical NF-kappaB signal transduction
  evidence_type: IMP
  original_reference_id: PMID:28362429
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1904178
    label: negative regulation of adipose tissue development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:30718772
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:31314592
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:1904238
    label: pericyte cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IDA
  original_reference_id: PMID:31146003
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IMP
  original_reference_id: PMID:27506447
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:27506447
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:27506447
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0002357
    label: defense response to tumor cell
  evidence_type: IMP
  original_reference_id: PMID:30429596
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:24504023
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0002572
    label: pro-T cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1 acts in nucleus/chromatin as a pioneer/master transcription 
      factor that selects accessible and inaccessible binding sites and shapes 
      hematopoietic chromatin accessibility.
    action: ACCEPT
    reason: Retain as core because PU.1 occupies active chromatin domains, can 
      bind high-affinity sites in DNase-inaccessible regions, and controls 
      hematopoietic euchromatin accessibility and transcription-factor access 
      (PMID:23658224, PMID:33951726).
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
- term:
    id: GO:0002573
    label: myeloid leukocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:28111278
  qualifier: involved_in
  review:
    summary: PU.1 regulates hematopoietic lineage fate, especially 
      myeloid/macrophage, dendritic-cell, and B-cell development.
    action: ACCEPT
    reason: Retain as core or near-core developmental biology because PU.1 
      deficiency or mutation disrupts lymphoid and myeloid development, while 
      iPSC macrophage differentiation is SPI1-dependent (PMID:28111278, 
      PMID:33951726).
- term:
    id: GO:1904151
    label: positive regulation of microglial cell mediated cytotoxicity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:31018969
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:31018969
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:31018969
  qualifier: involved_in
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0006357
      label: regulation of transcription by RNA polymerase II
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0140311
    label: protein sequestering activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0042826
    label: histone deacetylase binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0043314
    label: negative regulation of neutrophil degranulation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0120186
    label: negative regulation of protein localization to chromatin
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This annotation is a narrow disease, cell-line, high-throughput, or
      non-core downstream context and does not define SPI1/PU.1 core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the reviewed evidence supports PU.1 
      as a hematopoietic ETS transcription factor, while this term is 
      peripheral, context-specific, or too downstream for core function 
      curation.
- term:
    id: GO:1905036
    label: positive regulation of antifungal innate immune response
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:29290617
  qualifier: involved_in
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
- term:
    id: GO:0090402
    label: oncogene-induced cell senescence
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:1900745
    label: positive regulation of p38MAPK cascade
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: ISA
  original_reference_id: GO_REF:0000113
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: ISA
  original_reference_id: GO_REF:0000113
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IDA
  original_reference_id: PMID:24429361
  qualifier: part_of
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:24429361
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0070102
    label: interleukin-6-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:24429361
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:20139074
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20972335
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26019275
  qualifier: enables
  review:
    summary: The cited interaction reflects PU.1 cooperation with transcription 
      factors or transcriptional cofactors rather than generic protein binding.
    action: MODIFY
    reason: Modify generic protein binding to transcription-factor/cofactor 
      binding where the evidence supports PU.1 physical or functional 
      interaction with another transcriptional regulator.
    proposed_replacement_terms:
    - id: GO:0140297
      label: DNA-binding transcription factor binding
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9617064
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9617207
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0051525
    label: NFAT protein binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: PU.1 physically or functionally cooperates with transcription 
      factors and chromatin/transcriptional cofactors.
    action: ACCEPT
    reason: Retain because PU.1 function includes cooperative binding with other
      transcriptional regulators and cofactors at hematopoietic regulatory 
      elements (PMID:23658224, PMID:33951726).
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:15304486
  qualifier: located_in
  review:
    summary: PU.1 is a nuclear/chromatin transcription factor.
    action: ACCEPT
    reason: Retain because PU.1 functions in the nucleus, nucleoplasm, 
      chromatin, and transcription-regulator complexes to bind regulatory DNA 
      and control gene expression (PMID:2180582, PMID:23658224, PMID:33951726).
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:20139074
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:12833137
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
- term:
    id: GO:0045646
    label: regulation of erythrocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:12833137
  qualifier: involved_in
  review:
    summary: This lineage or immune-cell phenotype is compatible with PU.1 
      biology but is downstream or cell-type-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it reflects a particular hematopoietic, 
      immune, inflammatory, or disease-context outcome of PU.1 transcriptional 
      control rather than the defining DNA-binding/chromatin-regulatory 
      molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10207087
  qualifier: enables
  review:
    summary: The cached abstract is abstract-only or focused on another 
      ETS/fusion context and does not expose enough evidence to verify the 
      SPI1-specific interaction.
    action: UNDECIDED
    reason: Use UNDECIDED rather than removing the experimental annotation 
      because the curator may have used full-text evidence not present in the 
      cache; the abstract alone does not establish this SPI1-specific generic 
      protein-binding assertion.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: TAS
  original_reference_id: PMID:10867017
  qualifier: involved_in
  review:
    summary: PU.1/SPI1 is an ETS-domain transcription factor that binds 
      PU-box/cis-regulatory DNA motifs and activates or represses RNA polymerase
      II transcription.
    action: ACCEPT
    reason: Retain as core because PU.1 recognizes the 5'-GAGGAA-3' PU-box/ETS 
      motif, binds cis-regulatory regions in vivo, and controls hematopoietic 
      gene expression as a DNA-binding transcription factor (PMID:2180582, 
      PMID:23658224, PMID:33951726).
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: TAS
  original_reference_id: PMID:10867017
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: TAS
  original_reference_id: PMID:2180582
  qualifier: enables
  review:
    summary: The annotation is directionally correct but too broad for PU.1; the
      specific biology is RNA polymerase II cis-regulatory DNA binding and 
      transcription factor activity.
    action: MODIFY
    reason: Modify to a more informative PU.1 transcription-factor term because 
      generic DNA binding or DNA-templated transcription regulation obscures the
      ETS-domain cis-regulatory/RNA polymerase II mechanism.
    proposed_replacement_terms:
    - id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000113
  title: Gene Ontology annotation of human sequence-specific DNA binding 
    transcription factors (DbTFs) based on the TFClass database
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10207087
  title: 'Functional and physical interactions between AML1 proteins and an ETS protein,
    MEF: implications for the pathogenesis of t(8;21)-positive leukemias.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Cached abstract centers on MEF/AML1 interactions; 
      SPI1-specific protein-binding support is not visible in the cached 
      abstract.
- id: PMID:10867017
  title: The hematopoietic transcription factor PU.1 represses gelatinase A 
    transcription in glomerular mesangial cells.
  findings: []
- id: PMID:12833137
  title: 'CDK6 blocks differentiation: coupling cell proliferation to the block to
    differentiation in leukemic cells.'
  findings: []
- id: PMID:15304486
  title: Essential role of p38 mitogen-activated protein kinase in cathepsin K 
    gene expression during osteoclastogenesis through association of NFATc1 and 
    PU.1.
  findings: []
- id: PMID:18250304
  title: Gain-of-function mutation of GATA-2 in acute myeloid transformation of 
    chronic myeloid leukemia.
  findings: []
- id: PMID:18692240
  title: Physical and functional interactions between hematopoietic 
    cell-specific ETS transcription factors and homeodomain proteins.
  findings: []
- id: PMID:20139074
  title: Metallothionein-1 isoforms and vimentin are direct PU.1 downstream 
    target genes in leukemia cells.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached abstract supports PU.1 binding to CpG-rich target 
      promoters and both positive and negative transcriptional regulatory roles 
      in leukemia cells.
- id: PMID:20159610
  title: PML/RARalpha targets promoter regions containing PU.1 consensus and 
    RARE half sites in acute promyelocytic leukemia.
  findings: []
- id: PMID:20972335
  title: Hypoxia-induced microRNA-424 expression in human endothelial cells 
    regulates HIF-Ξ± isoforms and promotes angiogenesis.
  findings: []
- id: PMID:21575865
  title: Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in 
    ETS gene fusion-positive prostate cancer.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Cached abstract centers on ETS fusion-positive prostate cancer
      and PARP/DNA-PK interactions; SPI1-specific support is not visible in the 
      cached abstract.
- id: PMID:2180582
  title: The macrophage and B cell-specific transcription factor PU.1 is related
    to the ets oncogene.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract directly establishes PU.1 as a 
      macrophage/B-cell ETS DNA-binding transcriptional activator recognizing 
      the PU-box motif.
- id: PMID:24429361
  title: Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and 
    miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in 
    hepatitis.
  findings: []
- id: PMID:24504023
  title: Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 
    1 (HSF1) during macrophage differentiation of monocytes.
  findings: []
- id: PMID:26019275
  title: A Novel In-Frame Deletion in the Leucine Zipper Domain of C/EBPΞ΅ Leads 
    to Neutrophil-Specific Granule Deficiency.
  findings: []
- id: PMID:27506447
  title: Transcriptional regulation of the proto-oncogene Zfp521 by SPI1 (PU.1) 
    and HOXC13.
  findings: []
- id: PMID:28111278
  title: Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny 
    with MYB-Independent Tissue-Resident Macrophages.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached full text supports SPI1 dependence of human 
      iPSC-derived monocyte/macrophage development and relevance to 
      tissue-resident macrophages including microglia.
- id: PMID:28362429
  title: PU.1 supports TRAIL-induced cell death by inhibiting NF-ΞΊB-mediated 
    cell survival and inducing DR5 expression.
  findings: []
- id: PMID:28481873
  title: Restoring PU.1 induces apoptosis and modulates viral transactivation 
    via interferon-stimulated genes in primary effusion lymphoma.
  findings: []
- id: PMID:29290617
  title: METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and 
    Promotes Leukemogenesis via mRNA m(6)A Modification.
  findings: []
- id: PMID:30429596
  title: In vitro conversion of adult murine endothelial cells to hematopoietic 
    stem cells.
  findings: []
- id: PMID:30718772
  title: A transcription factor PU.1 is critical for Ccl22 gene expression in 
    dendritic cells and macrophages.
  findings: []
- id: PMID:31018969
  title: A Recurrent Activating Missense Mutation in WaldenstrΓΆm 
    Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor 
    SPI1 and Enhances Proliferation.
  findings: []
- id: PMID:31146003
  title: Androgen upregulates NR4A1 via the TFAP2A and ETS signaling networks.
  findings: []
- id: PMID:31314592
  title: PU.1 plays a pivotal role in dendritic cell migration from the 
    periphery to secondary lymphoid organs via regulating CCR7 expression.
  findings: []
- id: PMID:33951726
  title: Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia 
    patients.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached full text supports human SPI1/PU.1 chromatin 
      accessibility, DNA binding, nuclear localization, B-cell/dendritic-cell 
      deficiency, and early B/myeloid differentiation roles.
- id: Reactome:R-HSA-9617064
  title: SPI1 (PU.1), PML isoform 4, and EP300 bind the promoter of the CEBPE 
    gene
  findings: []
- id: Reactome:R-HSA-9617207
  title: SPI1 (PU.1), CEBPA and DEK bind the promoter of the CSF3R (G-CSFR) gene
  findings: []
- id: PMID:23658224
  title: Mechanisms of in vivo binding site selection of the hematopoietic 
    master transcription factor PU.1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached full text supports PU.1 in vivo binding-site selection,
      chromatin-domain accessibility, motif affinity, and cooperative 
      transcription-factor binding.
core_functions:
- description: ETS-domain cis-regulatory DNA binding and RNA polymerase II 
    transcription-factor activity at PU-box/ETS motifs in hematopoietic 
    regulatory elements.
  supported_by:
  - reference_id: PMID:2180582
    supporting_text: the PU.1 protein recognized a purine-rich sequence, 
      5'-GAGGAA-3' (PU box)
  - reference_id: PMID:2180582
    supporting_text: The PU.1 protein was shown to be a transcriptional 
      activator that is expressed in macrophages and B cells
  - reference_id: PMID:23658224
    supporting_text: PU.1 selects its binding sites primarily based on sequence 
      affinity
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  - id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  - id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0000785
    label: chromatin
- description: Pioneer/chromatin-regulatory activity that opens or selects 
    hematopoietic regulatory chromatin and permits cooperative 
    transcription-factor access.
  supported_by:
  - reference_id: PMID:23658224
    supporting_text: Occupied sites were predominantly detected in active 
      chromatin domains
  - reference_id: PMID:33951726
    supporting_text: decompacting stem cell heterochromatin and allowing 
      nonpioneer TFs to enter
  - reference_id: PMID:33951726
    supporting_text: destabilized PU.1 proteins unable to nuclear localize or 
      bind target DNA
  molecular_function:
    id: GO:0003682
    label: chromatin binding
  directly_involved_in:
  - id: GO:0045815
    label: transcription initiation-coupled chromatin remodeling
  - id: GO:0030154
    label: cell differentiation
  locations:
  - id: GO:0000785
    label: chromatin
  - id: GO:0005634
    label: nucleus
- description: Hematopoietic lineage specification and differentiation, 
    especially B-cell, myeloid/macrophage, dendritic-cell, and microglia-related
    macrophage programs, through PU.1-dependent transcriptional control.
  supported_by:
  - reference_id: PMID:33951726
    supporting_text: Affected patients lacked circulating B cells and possessed 
      few conventional dendritic cells
  - reference_id: PMID:33951726
    supporting_text: mutations into human hematopoietic stem and progenitor 
      cells impaired early in vitro B cell and myeloid cell differentiation
  - reference_id: PMID:28111278
    supporting_text: human iPSC-derived monocytes/macrophages develop in an 
      MYB-independent, RUNX1-, and SPI1 (PU.1)-dependent fashion
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0002573
    label: myeloid leukocyte differentiation
  - id: GO:0045579
    label: positive regulation of B cell differentiation
  - id: GO:1905453
    label: regulation of myeloid progenitor cell differentiation
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0000785
    label: chromatin
suggested_questions:
- question: Which SPI1-dependent microglial terms should be curated as direct 
    lineage-maintenance functions rather than downstream immune-cell outcomes?
- question: Can full-text evidence for the abstract-only ETS-family interaction 
    annotations be reviewed to decide whether SPI1-specific protein-binding 
    assertions should be accepted or removed?
suggested_experiments:
- hypothesis: Alzheimer-associated SPI1 regulatory variation alters PU.1 
    occupancy and chromatin accessibility in microglia.
  description: Perform matched PU.1 ChIP-seq/CUT&RUN and ATAC-seq in primary or 
    iPSC-derived human microglia carrying relevant SPI1 regulatory haplotypes.
  experiment_type: microglial chromatin profiling
- hypothesis: PU.1 dosage controls distinct B-cell and microglial target-gene 
    programs through shared ETS motif occupancy but different cooperative 
    factors.
  description: Compare SPI1 titration or degron perturbation across human B-cell
    precursors and microglia-like cells with RNA-seq and chromatin accessibility
    readouts.
  experiment_type: dose-response perturbation genomics