IRF8 (Interferon Regulatory Factor 8, also known as ICSBP) is a transcription factor of the IRF family that binds to interferon-stimulated response elements (ISRE), EICE (ETS-IRF composite elements with PU.1), and AICE (AP-1-IRF composite elements with BATF/JUN). It functions as both a transcriptional activator and repressor depending on context and binding partners. IRF8 is essential for myeloid and dendritic cell lineage specification, particularly for the development of plasmacytoid DCs (pDCs) and conventional DC1s (cDC1s). It regulates interferon and TLR signaling pathways and controls MHC class II antigen processing genes. Loss-of-function mutations cause immunodeficiency with dendritic cell and monocyte deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002376 immune system process | IBA GO_REF:0000033 | ACCEPT | Summary: IRF8 is a key transcription factor for immune system development and function. It is essential for myeloid and dendritic cell lineage specification [PMID:8861914], regulates interferon responses [PMID:1460054], and controls genes involved in antigen presentation [deep research: Qiu et al. 2024]. The IBA annotation reflects its well-established role across the IRF family. Reason: IRF8 is a master regulator of immune cell development and function. Knockout mice show immunodeficiency and deregulated hematopoiesis [PMID:8861914]. Human mutations cause dendritic cell immunodeficiency [PMID:25122610]. This broad process term appropriately captures IRF8's role. Supporting Evidence: PMID:8861914 Mice with a null mutation of ICSBP exhibit two prominent phenotypes related to previously described activities of the IRF family. The first is enhanced susceptibility to virus infections associated with impaired production of IFN(gamma). PMID:25122610 Laboratory evaluation revealed a highly unusual myeloid compartment, remarkable for the complete absence of CD141 and CD161 monocytes, absence of CD11c1 conventional dendritic cells (DCs) and CD11c1/CD1231 plasmacytoid DCs, and striking granulocytic hyperplasia. file:human/IRF8/IRF8-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IRF8 is a nuclear transcription factor that binds DNA regulatory elements. Nuclear localization is essential for its function and is well-documented [PMID:25122610, PMID:1460054]. Reason: IRF8 functions as a nuclear transcription factor. UniProt confirms nuclear localization [ECO:0000269|PubMed:23166356, ECO:0000269|PubMed:25122610]. The K108E mutation causes loss of nuclear localization, demonstrating the importance of nuclear translocation for function. Supporting Evidence: PMID:25122610 loss of the positively charged side chain at K108 causes loss of nuclear localization and loss of transcriptional activity |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: IRF8 regulates transcription by RNA polymerase II, acting both as an activator and repressor of target genes including interferon-inducible genes and immune cell differentiation genes [PMID:1460054]. Reason: IRF8 is a sequence-specific DNA-binding transcription factor that regulates Pol II transcription. The original 1992 paper established it as a negative regulator of ICS-containing promoters. It can both activate and repress transcription depending on context. Supporting Evidence: PMID:1460054 The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: IRF8 is a DNA-binding transcription factor with an N-terminal DNA-binding domain (IRF tryptophan pentad repeat) that binds ISRE, EICE, and AICE regulatory elements [PMID:1460054, deep research]. Reason: This is a core function of IRF8. The DNA-binding domain is well-characterized (amino acids 7-114 per UniProt). IRF8 binds interferon consensus sequences and regulates Pol II transcription. Supporting Evidence: PMID:1460054 Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: IRF8 binds specific DNA sequences including the interferon consensus sequence (ICS/ISRE), EICE (with PU.1), and AICE (with BATF/JUN) [PMID:1460054, deep research]. Reason: Sequence-specific DNA binding is well-established for IRF8. The original cloning paper demonstrated binding to ICS elements. More recent work shows binding to composite EICE and AICE motifs with partner transcription factors. Supporting Evidence: PMID:1460054 A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro mapping. IRF8 binds cis-regulatory regions including ISRE, EICE, and AICE elements. Reason: This is a parent term of the more specific GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding). The IEA annotation is consistent with IRF8's known DNA-binding function and supported by IBA annotation to the child term. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA machine learning models, consistent with IBA annotation to the same term. Reason: This duplicates the IBA annotation to GO:0000978. The IEA evidence provides additional support from computational methods. Both are valid. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: General DNA binding annotation from combined IEA methods. IRF8 has a well-characterized DNA-binding domain (IRF tryptophan pentad repeat, aa 7-114). Reason: This is a parent term of the more specific sequence-specific DNA binding terms. While general, it is accurate. More specific child terms are also annotated. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for general transcription factor activity. IRF8 is a DNA-binding transcription factor that can activate or repress transcription. Reason: This is a parent term of GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific). Accurate but less specific than the IBA annotation. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for nuclear localization, consistent with IBA and IDA annotations to the same term. Reason: Duplicates IBA annotation. Nuclear localization is well-established for IRF8 as a transcription factor. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location vocabulary. IRF8 is found in cytoplasm in resting cells and translocates to nucleus upon IFN-gamma stimulation. Reason: UniProt states IRF8 localizes in the cytoplasm in resting macrophages and translocates to the nucleus upon IFN-gamma induction. This cytoplasmic localization is accurate for unstimulated cells. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro. IRF8 regulates transcription as a DNA-binding transcription factor. Reason: This is a parent term of GO:0006357 (regulation of transcription by RNA polymerase II). Consistent with IRF8's core function as a transcription factor. |
| GO:0006914 autophagy | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: IEA annotation based on UniProt keyword mapping. UniProt lists "Autophagy" as a keyword based on one paper [PMID:29434592] showing IRF8 positively regulates macroautophagy in dendritic cells. However, IRF8 is a transcription factor that may regulate autophagy gene expression, not a direct autophagy component. Reason: IRF8 is a transcription factor for immune cell differentiation, not an autophagy pathway component. The UniProt annotation is based on a single paper showing IRF8 can positively regulate autophagy in DCs, but this is a downstream effect of its transcription factor activity, not a core function. The term "autophagy" without qualifier implies direct involvement in the autophagy process. A more appropriate annotation would be "regulation of autophagy" if warranted. |
| GO:0006955 immune response | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA. IRF8 regulates immune responses through its role in interferon signaling and immune cell development. Reason: IRF8 is critical for immune responses, controlling interferon-inducible gene expression and immune cell differentiation. This is consistent with the IBA annotation to GO:0002376 (immune system process). |
| GO:0098542 defense response to other organism | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation from ARBA. IRF8 is important for defense against pathogens through its role in interferon responses and immune cell development. Reason: While IRF8 is important for antimicrobial defense (IRF8 mutations cause mycobacterial susceptibility), this is a downstream consequence of its role as a transcription factor for immune cell development, not a direct molecular function. Defense response is a secondary process. Supporting Evidence: PMID:8861914 enhanced susceptibility to virus infections associated with impaired production of IFN(gamma) |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI annotation from HI5 interactome mapping study. This was a high-throughput proteomics study mapping innate immunity protein interactions. IRF8 was one of many proteins analyzed. Reason: "Protein binding" (GO:0005515) is uninformative without specifying the binding partner or functional context. The HI5 study was a high-throughput interactome mapping that does not provide specific functional insights for IRF8. More informative annotations for IRF8's protein interactions exist (e.g., with PU.1, BATF, JUNB). This vague annotation should be replaced with specific partner annotations. Supporting Evidence: PMID:21903422 2011 Sep 8. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: IPI annotation from a neurodegenerative disease interactome mapping study that included IRF8 as one of many proteins analyzed via yeast two-hybrid. Reason: This high-throughput interactome study focused on neurodegenerative disease proteins. IRF8 is not a neurodegeneration protein; it is an immune transcription factor. The "protein binding" annotation from this study provides no meaningful functional information about IRF8's actual binding partners (PU.1, BATF, JUNB, etc.). Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for transcriptional repression. IRF8 was originally identified as a negative regulator of ICS-containing promoters [PMID:1460054]. Reason: IRF8 acts as a transcriptional repressor in certain contexts, including repression of interferon-inducible genes and osteoclast differentiation factors. This is well-documented experimentally and supported by IDA annotations. Supporting Evidence: PMID:1460054 ICSBP acts as a negative regulatory factor on ICS-containing promoters |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from Ensembl Compara ortholog transfer. IRF8 binds specific DNA sequences in transcription regulatory regions. Reason: Equivalent to GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding). Consistent with IBA and IDA annotations to related terms. IRF8 binds ISRE, EICE, and AICE elements. |
| GO:0002273 plasmacytoid dendritic cell differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from ortholog transfer. IRF8 is essential for pDC development, as demonstrated by loss of pDCs in IRF8-deficient mice and humans [PMID:25122610, file:human/IRF8/IRF8-deep-research-falcon.md]. Reason: This is a core function of IRF8. Human patients with IRF8 mutations lack circulating pDCs. Mouse knockouts also lack pDCs. This is well-supported by both human and mouse studies. Supporting Evidence: PMID:25122610 Laboratory evaluation revealed a highly unusual myeloid compartment, remarkable for the complete absence of CD141 and CD161 monocytes, absence of CD11c1 conventional dendritic cells (DCs) and CD11c1/CD1231 plasmacytoid DCs, and striking granulocytic hyperplasia. |
| GO:0002314 germinal center B cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation from ortholog transfer. IRF8 is expressed in B cells and involved in B cell development, including germinal center reactions. Reason: IRF8 is expressed in B cells and plays roles in B cell biology, but its primary functions are in myeloid and dendritic cell lineages. B cell differentiation is a secondary role. The deep research mentions IRF8 involvement in germinal center programs and B cell lymphoma antigen presentation, but myeloid/DC specification is the core function. |
| GO:0002316 follicular B cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation from ortholog transfer for follicular B cell differentiation. Reason: Similar to germinal center B cell differentiation - IRF8 has roles in B cell biology but its core functions are in myeloid/DC lineage specification. This represents a secondary function in B cell development. |
| GO:0032479 regulation of type I interferon production | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from ortholog transfer. IRF8 regulates type I interferon responses through its role in pDC development (major IFN-I producers) and direct transcriptional regulation. Reason: IRF8 is essential for pDC development, and pDCs are the major producers of type I interferons. Additionally, IRF8 directly regulates interferon-inducible genes. This is a well-established function. Supporting Evidence: PMID:1460054 The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation from ortholog transfer for apoptosis regulation. Reason: IRF8 has been implicated in apoptosis regulation in some contexts, but this is not a core function. Its primary roles are in transcriptional regulation of immune cell differentiation and interferon responses. Apoptosis effects may be secondary consequences. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for transcriptional activation. IRF8 can act as a transcriptional activator in certain contexts, particularly for immune response genes. Reason: IRF8 functions as both activator and repressor depending on context. UniProt states it "Can both act as a transcriptional activator or repressor." The K108E mutation causes loss of transcriptional activity, demonstrating wild-type IRF8 has activator function. Supporting Evidence: PMID:25122610 Biochemical characterization of the IRF8(K108E) mutant in vitro shows that loss of the positively charged side chain at K108 causes loss of nuclear localization and loss of transcriptional activity |
| GO:0071346 cellular response to type II interferon | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from ortholog transfer. IRF8 expression is induced by IFN-gamma and it mediates IFN-gamma transcriptional responses [PMID:1460054]. Reason: IRF8 is induced by IFN-gamma and translocates to the nucleus upon IFN-gamma stimulation to regulate target genes. IFN treatment alleviates ICSBP-mediated repression. Supporting Evidence: PMID:1460054 either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP |
| GO:0097028 dendritic cell differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from ortholog transfer. IRF8 is essential for dendritic cell development, particularly cDC1 and pDC lineages [PMID:25122610, deep research]. Reason: This is a core function of IRF8. Human IRF8 mutations cause DC deficiency. Mouse knockouts lack cDC1 and pDC populations. IRF8 programs enhancers for DC lineage specification. Supporting Evidence: PMID:25122610 absence of CD11c1 conventional dendritic cells (DCs) and CD11c1/CD1231 plasmacytoid DCs |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation from HPA immunofluorescence data. IRF8 localizes to the nucleoplasm as a transcription factor. Reason: As a DNA-binding transcription factor, IRF8 functions in the nucleoplasm where it binds chromatin. This is consistent with its molecular function. |
| GO:0005515 protein binding | IPI PMID:33951726 Constrained chromatin accessibility in PU.1-mutated agammagl... | MODIFY | Summary: IPI annotation for protein binding, specifically with PU.1/SPI1. The study characterized PU.1 mutations in agammaglobulinemia and showed IRF8 interaction with PU.1. Reason: While this annotation captures a real interaction, "protein binding" is too vague. IRF8 interacts with PU.1 to bind EICE composite elements and regulate gene expression. A more specific term like "DNA-binding transcription factor binding" or annotation with specific interaction context would be more informative. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:33951726 May 5. Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. |
| GO:0002273 plasmacytoid dendritic cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from manual ortholog transfer. pDC differentiation is essential function of IRF8. Reason: Duplicates the IEA annotation with different evidence (manual ortholog transfer). pDC differentiation is a well-established core function of IRF8. |
| GO:0032479 regulation of type I interferon production | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from manual ortholog transfer. IRF8 regulates type I IFN production. Reason: Duplicates the IEA annotation with different evidence. Type I IFN regulation is well-established. |
| GO:0097028 dendritic cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation from manual ortholog transfer. DC differentiation is a core IRF8 function. Reason: Duplicates the IEA annotation with different evidence. DC differentiation is a core function of IRF8 supported by human and mouse genetic evidence. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: IDA annotation from a systematic study of transcription factor DNA binding specificities using SELEX. The study examined 542 human TFs including IRF8. Reason: IRF8 binds specific DNA sequences (ISRE, EICE, AICE elements) as double-stranded DNA. This systematic study provides direct evidence for sequence-specific binding. Supporting Evidence: PMID:28473536 Impact of cytosine methylation on DNA binding specificities of human transcription factors. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: ISA annotation from TFClass database for transcription factors. IRF8 binds chromatin at regulatory elements. Reason: As a transcription factor, IRF8 functions at chromatin, binding enhancers and promoters. Deep research describes IRF8's role in chromatin accessibility and enhancer programming. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: ISA annotation from TFClass database. IRF8 is classified as a sequence-specific DNA-binding transcription factor. Reason: Duplicates IBA annotation. This is a core molecular function of IRF8. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:1460054 Human interferon consensus sequence binding protein is a neg... | ACCEPT | Summary: IDA annotation from the original IRF8/ICSBP cloning paper showing it acts as a transcriptional repressor of interferon-inducible genes. Reason: The original characterization paper demonstrated that ICSBP/IRF8 acts as a negative regulator of ICS-containing promoters. This is direct experimental evidence. Supporting Evidence: PMID:1460054 The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:25122610 Functional characterization of the human dendritic cell immu... | ACCEPT | Summary: IDA annotation from functional characterization of human IRF8 K108E mutation showing loss of transcriptional activity. Reason: The study characterized IRF8 function by showing that the K108E mutation causes loss of transcriptional activity, demonstrating that wild-type IRF8 has transcriptional regulatory function. Supporting Evidence: PMID:25122610 Biochemical characterization of the IRF8(K108E) mutant in vitro shows that loss of the positively charged side chain at K108 causes loss of nuclear localization and loss of transcriptional activity |
| GO:0005634 nucleus | IDA PMID:25122610 Functional characterization of the human dendritic cell immu... | ACCEPT | Summary: IDA annotation for nuclear localization from the K108E mutation study showing IRF8 requires nuclear localization for function. Reason: Direct experimental evidence for nuclear localization and its importance for function. The K108E mutation causes loss of nuclear localization. Supporting Evidence: PMID:25122610 loss of the positively charged side chain at K108 causes loss of nuclear localization and loss of transcriptional activity |
| GO:0005737 cytoplasm | IDA PMID:25122610 Functional characterization of the human dendritic cell immu... | ACCEPT | Summary: IDA annotation for cytoplasmic localization in resting cells before IFN-gamma stimulation. Reason: IRF8 is found in the cytoplasm in resting cells. The K108E mutation affects nuclear translocation, indicating normal IRF8 shuttles between cytoplasm and nucleus. Supporting Evidence: PMID:25122610 Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8(K108E) mutation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:25122610 Functional characterization of the human dendritic cell immu... | ACCEPT | Summary: IDA annotation for transcriptional activation function, demonstrated by loss of transcriptional activity in K108E mutant. Reason: The K108E mutation study showed loss of transcriptional activity, demonstrating that wild-type IRF8 can activate transcription. Supporting Evidence: PMID:25122610 loss of the positively charged side chain at K108 causes loss of nuclear localization and loss of transcriptional activity |
| GO:0071346 cellular response to type II interferon | IDA PMID:25122610 Functional characterization of the human dendritic cell immu... | ACCEPT | Summary: IDA annotation for IFN-gamma response, showing IRF8 is involved in interferon-regulated transcription. Reason: The study shows IRF8 regulates IRF8-bound and IRF8-regulated transcriptional targets that are depleted in the patient, demonstrating its role in interferon responses. Supporting Evidence: PMID:25122610 depletion of IRF8-bound and IRF8-regulated transcriptional targets |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:1460054 Human interferon consensus sequence binding protein is a neg... | ACCEPT | Summary: IDA annotation for sequence-specific DNA binding to the interferon consensus sequence (ICS). Reason: The original cloning paper demonstrated that ICSBP binds to ICS elements and that truncation of the N-terminus eliminates DNA binding. Supporting Evidence: PMID:1460054 Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:1460054 Human interferon consensus sequence binding protein is a neg... | ACCEPT | Summary: IDA annotation for transcriptional repressor activity based on the original cloning paper. Reason: The original paper established ICSBP/IRF8 as a transcriptional repressor of ICS-containing promoters. This molecular function is well-documented. Supporting Evidence: PMID:1460054 ICSBP acts as a negative regulatory factor on ICS-containing promoters |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1015702 | ACCEPT | Summary: TAS annotation from Reactome pathway for expression of IFN-induced genes. IRF8 is present in cytosol in unstimulated cells. Reason: Consistent with IDA annotation showing cytoplasmic localization in resting cells. Cytosol is a subcompartment of cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1031716 | ACCEPT | Summary: TAS annotation from Reactome pathway for expression of IFNG-stimulated genes. Reason: Duplicate of above annotation from different Reactome pathway. Cytosolic localization is consistent with other evidence. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS PMID:1460054 Human interferon consensus sequence binding protein is a neg... | ACCEPT | Summary: TAS annotation for transcriptional repression, citing the original ICSBP cloning paper. Reason: This is a duplicate of the IDA annotation to the same term from the same reference. The original paper established IRF8 as a transcriptional repressor. Supporting Evidence: PMID:1460054 Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | TAS PMID:1460054 Human interferon consensus sequence binding protein is a neg... | ACCEPT | Summary: TAS annotation for transcription factor activity from the original cloning paper. Reason: This duplicates IBA and ISA annotations. The original paper established IRF8 as a DNA-binding transcription factor. Supporting Evidence: PMID:1460054 Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. |
| GO:0006955 immune response | TAS PMID:8861914 Immunodeficiency and chronic myelogenous leukemia-like syndr... | ACCEPT | Summary: TAS annotation for immune response based on the mouse knockout study showing immunodeficiency. Reason: The mouse knockout study demonstrated IRF8's essential role in immune function, including virus susceptibility and impaired IFN-gamma production. Supporting Evidence: PMID:8861914 enhanced susceptibility to virus infections associated with impaired production of IFN(gamma) |
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Download this section (compressed HTML)Q: What are the specific enhancer elements and chromatin accessibility changes controlled by IRF8 in human DC progenitors?
Q: How do IRF8 interactions with different partners (PU.1 vs BATF) determine activator vs repressor function?
Q: What is the relationship between IRF8 and MHC class II antigen processing gene regulation in human DCs?
Experiment: ChIP-seq analysis of IRF8 binding sites in human monocyte-derived DCs with and without IFN-gamma stimulation
Experiment: CRISPR screens in human hematopoietic progenitors to identify IRF8-dependent genes for DC differentiation
Experiment: Structural studies of IRF8-DNA-partner complexes to understand composite element recognition
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