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.
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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. Proposed replacements: regulation of transcription by RNA polymerase II |
| 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. Proposed replacements: cis-regulatory region sequence-specific DNA binding |
| 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. Proposed replacements: DNA-binding transcription factor binding |
| 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. Proposed replacements: DNA-binding transcription factor binding |
| 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. Proposed replacements: DNA-binding transcription factor binding |
| 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. Proposed replacements: cis-regulatory region sequence-specific DNA binding |
| 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. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| 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. Proposed replacements: negative regulation of transcription by RNA polymerase II |
| 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. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| 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. Proposed replacements: DNA-binding transcription factor binding |
| 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. Proposed replacements: cis-regulatory region sequence-specific DNA binding |
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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. Proposed replacements: regulation of transcription by RNA polymerase II |
| 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. Proposed replacements: negative regulation of transcription by RNA polymerase II |
| 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. Proposed replacements: DNA-binding transcription factor binding |
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
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Download this section (compressed HTML)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?
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
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