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FLASH GENE
Symbol IRF8 contributors: mct/npt/pgu - updated : 11-06-2016
HGNC name interferon regulatory factor 8
HGNC id 5358
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 2678 - 426 - 1995 7768900
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node   highly
 spleen   lowly
 thymus   moderately
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunelymphocyte
cell lineage
cell lines
fluid/secretion blood
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a conserved DNA-binding domain in the N-terminal region, (AAs 1-121) when fused in frame to the transcriptional activation domain of the herpes simplex VP16 (ICSBP-VP16) is a very strong activator of ICS-containing promoters
  • a third functional domain that enables the association with IRFs
  • a divergent C-terminal region that serves as the regulatory domain
  • HOMOLOGY
    interspecies ortholog to murine Icsbp1
    Homologene
    FAMILY
  • interferon (IFN) regulatory factor (IRF) family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • regulating expression of genes stimulated by type I IFNs, namely IFN-alpha and IFN-beta
  • also controling expression of IFN-alpha and IFN-beta-regulated genes that are induced by viral infection
  • acts as a repressor of interferon consensus sequence (ICS) containing promoters that can be alleviated by interferons
  • playing a negative regulatory role in cells of the immune system
  • with IRF4 are dichotomous regulators of transcription in macrophages
  • playing a role in regulating the proliferation and differentiation of hematopoietic progenitor cells
  • IRF8-induced PTPN13 repression occurred in granulocyte/monocyte progenitor cells, and this activity increased during myeloid differentiation
  • interferon regulatory transcription factor with leukemia-suppressor activity
  • regulates genes that are involved in phagocyte function, proliferation, and apoptosis
  • transcription factor expressed in immune cells, and a key regulatory molecule for osteoclastogenesis
  • inhibits osteoclast formation under physiological and pathological conditions, suggesting a model where downregulation of inhibitory factors such as IRF8 contributes to TNFSF11-mediated osteoclastogenesis
  • contributing to B cell development from hematopoietic stem cells in the bone marrow and implicated in the hierarchical regulatory network governing specification and commitment to the B cell fate
  • functions in the GC B-cell transcription program and directly stimulates expression of the BCL6 gene
  • key transcription factor for myeloid cell differentiation
  • regulates ASAH1 expression to mediate apoptosis and suppresses myelogeneous leukemia
  • interferon regulatory transcription factor with leukemia suppressor activity
  • activates some target genes in myeloid progenitor cells and other target genes in mature phagocytes
  • IRF8, ETV6 and HDAC3 cooperated to increase sensitivity to FAS-induced apoptosis
  • during normal myelopoiesis, is involved in activation of phagocyte-specific genes, proliferation arrest, and increased sensitivity to FAS-induced apoptosis
  • IRF5 and IRF8, two transcription factors with opposing functions, control TLR9 signaling in human plasmacytoid dendritic cells (pDCs)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS immunity/defense
    text immune response
    PATHWAY
    metabolism
    signaling
    a component
  • complex comprising BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function
  • INTERACTION
    DNA binding to the IFN-stimulated response element (ISRE)
    RNA
    small molecule
    protein
  • TRIP15
  • FANCF is an IRF8 target gene
  • PTPN13 is an IRF8 target gene (interacted with a cis element in the proximal PTPN13 promoter and repressed transcription)
  • collaboration between IRF8 deficiency and MEIS1/MEIS3 in the acceleration of chronic myeloid leukemia-like disease
  • requirement for IRF3, a master regulator of IFNB1 production, as a previously un-indentified interaction partner of IRF8
  • IRF8 is critical for CST3 expression in primary dendritic cells
  • ASAH1 is a general transcription target of IRF8 (directly binds to the ASAH1 promoter)
  • PTPN13 is an IRF8 target (repression of PTPN13 by IRF8 requires cooperation with ETV6 and histone deacetylase 3)
  • ETV6 interacts with IRF proteins, including IRF8, and represses transcription of various target genes during normal myelopoiesis
  • ETV6-PDGFRB antagonizes the effects of ETV6 and IRF8 on PTPN13 transcription
  • IRF8 inhibits TLR9-dependent gene expression by directly blocking the activity of IRF5
  • more IRF8 bound to the IFN-stimulated response element of the IFIT1 gene than to those of the IFIT2 and the IFIT3 genes
  • IRF8 is required for optimal activation of the NLRC4 inflammasome in bone-marrow-derived macrophages infected with Salmonella Typhimurium
  • vitamin D regulation of ZMIZ1 and IRF8 in dendritic cells (DCs) and monocytes contribute to latitude-dependent autoimmune disease risk
  • cell & other
    REGULATION
    induced by interferon gamma
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in AML and chronic myeloid leukemia during blast crisis (CML-BC), and its deficiency may be functionally important for accumulation of chromosomal abnormalities during disease progression in these myeloid malignancies
    tumoral     --over  
    IRF8 and TNFSF13 expression was significantly higher in lymphomas with IGH rearrangements targeting these loci
    Susceptibility to systemic lupus erythematosus
    Variant & Polymorphism SNP
  • rs11648084 and rs11644034 associated to systemic lupus erythematosus
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmuneLupus
    IRF8 may provide important targets for therapeutic intervention in human lupus
    ANIMAL & CELL MODELS
  • Irf8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic myelogeneous leukemia (CML)