irf8 irf8 interferon regulatory factor 8 (irf8) also known as interferon consensus sequence-binding protein (icsbp), is a protein that in humans is encoded by the irf8 gene. irf8 is a transcription factor that plays critical roles in the regulation of lineage commitment and in myeloid cell maturation including the decision for a common myeloid progenitor (cmp) to differentiate into a monocyte precursor cell. irf8identifiersaliasesirf8, h-icsbp, icsbp, icsbp1, imd32a, imd32b, irf-8, interferon regulatory factor 8external idsomim: 601565 mgi: 96395 homologene: 1629 genecards: irf8 gene location (human)chr.chromosome 16 (human)band16q24.1start85,899,116 bpend85,922,606 bpgene location (mouse)chr.chromosome 8 (mouse)band8 e1|8 70.05 cmstart121,463,097 bpend121,483,433 bprna expression patternbgeehumanmouse (ortholog)top expressed inmonocytelymph nodespleensecondary oocyteappendixbloodbone marrowrectumcancellous boneduodenumtop expressed inspleenbone marrowsubmandibular glandcrypt of lieberkuhn of small intestinejejunumsubcutaneous adipose tissuebloodpaneth cellduodenumthymusmore reference expression databiogpsmore reference expression datagene ontologymolecular function dna binding dna-binding transcription factor activity protein binding transcription factor activity, rna polymerase ii distal enhancer sequence-specific binding rna polymerase ii transcription regulatory region sequence-specific dna binding rna polymerase ii cis-regulatory region sequence-specific dna binding dna-binding transcription repressor activity, rna polymerase ii-specific dna-binding transcription factor activity, rna polymerase ii-specific cellular component cytosol nucleoplasm nucleus cytoplasm biological process myeloid cell differentiation regulation of transcription, dna-templated response to bacterium positive regulation of interleukin-12 production interferon-gamma-mediated signaling pathway positive regulation of interferon-gamma production positive regulation of transcription initiation from rna polymerase ii promoter transcription, dna-templated positive regulation of transcription, dna-templated defense response to bacterium type i interferon signaling pathway immune response phagocytosis cellular response to lipopolysaccharide defense response to protozoan negative regulation of transcription by rna polymerase ii positive regulation of transcription by rna polymerase ii cellular response to interferon-gamma autophagy immune system process sources:amigo / quickgoorthologsspecieshumanmouseentrez339415900ensemblensg00000140968ensmusg00000041515uniprotq02556p23611refseq (mrna)nm_002163nm_001363907nm_001363908nm_001301811nm_008320refseq (protein)np_002154np_001350836np_001350837np_001288740np_032346location (ucsc)chr 16: 85.9 – 85.92 mbchr 8: 121.46 – 121.48 mbpubmed searchwikidataview/edit humanview/edit mouse function interferon consensus sequence-binding protein (icsbp) is a transcription factor of the interferon regulatory factor (irf) family. proteins of this family are composed of a conserved dna-binding domain in the n-terminal region and a divergent c-terminal region that serves as the regulatory domain. the irf family proteins bind to the ifn-stimulated response element (isre) and regulate expression of genes stimulated by type i ifns, namely ifn-α and ifn-β. irf family proteins also control expression of ifn-α and ifn-β-regulated genes that are induced by viral infection. knockout studies ifn-producing cells (mipcs) were absent in all lymphoid organs from icsbp knockout (ko) mice, as revealed by lack of cd11clowb220+ly6c+cd11b− cells. in parallel, cd11c+ cells isolated from icsbp ko spleens were unable to produce type i ifns in response to viral stimulation. icsbp ko mice also displayed a marked reduction of the dc subset expressing the cd8alpha marker (cd8alpha+ dcs) in spleen, lymph nodes, and thymus. moreover, icsbp-deficient cd8alpha+ dcs exhibited a markedly impaired phenotype when compared with wt dcs. they expressed very low levels of costimulatory molecules (intercellular adhesion molecule icam1, cd40, cd80, cd86) and of the t cell area-homing chemokine receptor ccr7. clinical significance in myeloid cells, irf8 regulates the expression of bax and fas to regulate apoptosis. in chronic myelogenous leukemia (cml), irf8 regulates acid ceramidase to mediate cml apoptosis. irf8 is highly expressed in myeloid cells and was originally identified in as a critical lineage-specific transcription factor for myeloid cell differentiation, recent studies, however, have shown that irf8 is also constitutively expressed in non-hematopoietic cancer cells, albeit at a lower level. furthermore, irf8 can also be up-regulated by ifn-γ in non-hemotopoietic cells. irf8 mediates the expression of fas, bax, flip, jak1 and stat1 to mediate apoptosis in non-hemotopoietic cancer cells. analysis of human cancer genomics database revealed that irf8 is not significantly focally amplified across the entire dataset of 3131 tumors, but is significantly focally deleted across the entire dataset of 3131 tumors, suggesting that irf8 is potentially a tumor suppressor in humans. molecular analysis indicated that the irf8 gene promoter is hypermethylated in human colon carcinoma cells, suggesting that these cells might use dna methylation to silence irf8 expression to advance the disease. interactions irf8 has been shown to interact with irf1 and cops2.