Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Modulation of T cell cytokine production by interferon regulatory factor-4.
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IRF4 is lymphoid-restricted and its deficiency impairs CD4+ T cell cytokine production
"Interferon regulatory factor (IRF)-4 is a lymphoid-restricted member of the interferon regulatory factor family of transcriptional regulators, whose deficiency leads to a profound impairment in the ability of mature CD4(+) T cells to produce cytokines."
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Stable IRF4 expression in Jurkat T cells enhances IL-2 and enables IL-4, IL-10, IL-13 production
"We demonstrate that stable expression of IRF-4 in Jurkat T cells not only leads to a strong enhancement in the synthesis of interleukin (IL)-2, but also enables these cells to start producing considerable amounts of IL-4, IL-10, and IL-13."
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IRF4 transactivates IL-2 and IL-4 promoter-reporter constructs
"Transient transfection assays indicate that IRF-4 can transactivate luciferase reporter constructs driven by either the human IL-2 or the human IL-4 promoter."
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IRF4 binds a site in the IL-4 promoter adjacent to an NFAT binding element and cooperates with NFATc1
"A detailed analysis of the effects of IRF-4 on the IL-4 promoter reveals that IRF-4 binds to a site adjacent to a functionally important NFAT binding element and that IRF-4 cooperates with NFATc1."
Defining the membrane proteome of NK cells.
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Proteomics study of NK cell membrane fractions identified 1843 proteins including IRF4
"The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes."
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Approximately 60% of identified proteins were not predicted membrane proteins
"approximately 40% of the identified proteins were predicted as plausible membrane proteins."
Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
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Large-scale interactome mapping (HI5) of innate immune signaling
"IKBKAP interacts with IRF4 and negatively regulates HSV-induced IFN production."
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IKBKAP (ELP1) interacts with IRF4 and negatively regulates HSV-induced IFN production
"IKBKAP interacts with IRF4 and negatively regulates HSV-induced IFN production."
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IRF4 interactions with IRAK1, TLK2, YTHDC2 detected
"Fifty-eight baits were associated with 260 interacting proteins forming a human innate immunity interactome for type I interferon (HI5) of 401 unique interactions"
IRF4 is a key thermogenic transcriptional partner of PGC-1α.
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Mouse Irf4 promotes thermogenic gene expression in brown adipose tissue
"Here, we identify interferon regulatory factor 4 (IRF4) as a dominant transcriptional effector of thermogenesis. IRF4 is induced by cold and cAMP in adipocytes and is sufficient to promote increased thermogenic gene expression, energy expenditure, and cold tolerance."
Impact of cytosine methylation on DNA binding specificities of human transcription factors.
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Systematic SELEX analysis of 542 human TFs including IRF4
"By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences."
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Provided direct biochemical evidence of IRF4 sequence-specific DNA binding
"In this work, we performed systematic analysis of DNA binding specificities of full-length TFs and eDBDs using unmethylated and CpG-methylated DNA ligands."
IRF4 haploinsufficiency in a family with Whipple's disease.
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R98W variant causes loss of DNA-binding transcription activator activity
"We found that R98W was loss-of-function, modified the transcriptome of heterozygous leukocytes following Tw stimulation, and was not dominant-negative."
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RC98-99AA double mutant also loses activity
"IRF4 R98A-C99A, which is LOF for DNA binding (Brass et al., 1999), was included as a negative control."
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IRF4 haploinsufficiency causes combined immunodeficiency (IMD131)
"AD IRF4 deficiency can underlie WD by haploinsufficiency, with age-dependent incomplete penetrance."
A reference map of the human binary protein interactome.
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HuRI systematic yeast two-hybrid interactome mapping
"Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'."
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IRF4 interactions with GIPC2 and TSEN54 detected
"Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies."
Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.
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IRF4 directly interacts with PU.1 (SPI1)
"Consistent with intact PEST domains, all three proteins coimmunoprecipitated with IRF4 and IRF8 (Fig. S5 E)."
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PU.1 mutations impair chromatin accessibility in B cell development
"Once in open chromatin, PU.1 can directly control gene expression by binding genetic regulatory elements and can also more broadly influence transcription by recruiting nonpioneers, such as interferon regulatory factors (IRFs), to otherwise inaccessible genomic regions (Ciau-Uitz et al., 2013; Heinz et al., 2013; Pongubala and Atchison, 1997; Sherwood et al., 2014)."
A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency.
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T95R variant gains neomorphic DNA binding to GATA sequences
"IRF4T95R behaved as a gain-of-function hypermorph by binding to DNA with higher affinity than IRF4WT. Despite this increased affinity for DNA, the transcriptional activity on IRF4 canonical genes was reduced, showcasing a hypomorphic activity of IRF4T95R."
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Decreased activation from canonical ISRE reporter
"Simultaneously, IRF4T95R functions as a neomorph by binding to noncanonical DNA sites to alter the gene expression profile, including the transcription of genes exclusively induced by IRF4T95R but not by IRF4WT."
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Confirms wildtype IRF4 DNA-binding transcription activator activity
"Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function."
A neomorphic mutation in the interferon activation domain of IRF4 causes a dominant primary immunodeficiency.
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F359L variant loses DNA-binding transcription activator activity
"The mutant IRF4 failed to efficiently regulate the transcriptional activity of interferon-stimulated response elements (ISREs)."
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No effect on subcellular location (nucleus/cytoplasm)
"The IRF4 F359L and IRF4 WT proteins were similar with regard to their subcellular localization in the cytoplasm and the nucleus"
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Confirms wildtype IRF4 functions as transcriptional activator in nucleus
"Expression of the mutant IRF4 protein in control lymphoblastoid B cell lines reduced the expression of BLIMP-1 and XBP1 (key transcription factors in plasma cell differentiation)."
Expression of IFN-induced genes
Expression of IFNG-stimulated genes
Expression of STAT3-upregulated cytosolic proteins
NPM1-ALK- and p-STAT3-dependent IRF4 gene expression
IRF4 binds the TYR promoter
MITF-M-dependent IRF4 gene expression