Contents

IRF8

Protein-coding gene in the species Homo sapiens

IRF8
Identifiers
Aliases	IRF8, H-ICSBP, ICSBP, ICSBP1, IMD32A, IMD32B, IRF-8, interferon regulatory factor 8
External IDs	OMIM: 601565; MGI: 96395; HomoloGene: 1629; GeneCards: IRF8; OMA:IRF8 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q24.1 Start 85,899,116 bp[1] End 85,922,606 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 E1|8 70.05 cM Start 121,463,097 bp[2] End 121,483,433 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte lymph node spleen secondary oocyte appendix granulocyte blood epithelium of colon bone marrow rectum Top expressed in Ileal epithelium mesenteric lymph nodes spleen bone marrow tibiofemoral joint submandibular gland crypt of lieberkuhn of small intestine jejunum stroma of bone marrow subcutaneous adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular 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 / QuickGO
Orthologs Species Human Mouse Entrez 3394 15900 Ensembl ENSG00000140968 ENSMUSG00000041515 UniProt Q02556 P23611 RefSeq (mRNA) NM_002163 NM_001363907 NM_001363908 NM_001301811 NM_008320 RefSeq (protein) NP_002154 NP_001350836 NP_001350837 NP_001288740 NP_032346 Location (UCSC) Chr 16: 85.9 – 85.92 Mb Chr 8: 121.46 – 121.48 Mb PubMed search [3] [4]
Wikidata
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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.^[5][6][7] 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.

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.^[5]

Knockout studies

IFN-producing cells (mIPCs) were absent in all lymphoid organs from ICSBP knockout (KO) mice, as revealed by lack of CD11c^lowB220⁺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.^[8]

Clinical significance

In myeloid cells, IRF8 regulates the expression of Bax and Fas to regulate apoptosis.^[9]Inchronic myelogenous leukemia (CML), IRF8 regulates acid ceramidase to mediate CML apoptosis.^[10]

IRF8 is highly expressed in myeloid cells and was originally identified in as a critical lineage-specific transcription factor for myeloid cell differentiation,^[11] 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.^[12][13][14]

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.^[15] Molecular analysis indicated that the IRF8 gene promoter is hypermethylated in human colon carcinoma cells,^[14][16] 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^[17][18] and COPS2.^[19]

See also

• Interferon regulatory factors

References

Illustrations

Further reading

External links

• IRF8+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.