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FLASH GENE
Symbol HDAC3 contributors: mct/ - updated : 10-04-2019
HGNC name histone deacetylase 3
HGNC id 4854
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies ortholog to yeast Rpd3
Homologene
FAMILY
  • histone deacetylase family
  • type 1 subfamily
    • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • histone deacetyltransferase, modulator of chromatin structure
  • responsible for the deacetylase activities that are associated with HDAC4 and HDAC7
  • can function as the catalytic subunits of multiprotein complexes
  • activation of HDAC3 by NCOR1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology
  • central role in regulating the cell proliferation and differentiation of colon cancer cells, suggesting a potential mechanism by which colon cancers may become resistant to luminal butyrate
  • critical roles in S phase progression and DNA damage control
  • concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression
  • functions in the regulation of circadian rhythm and glucose metabolism
  • selectively represses CREB3-mediated transcriptional activation and chemotactic signaling in human metastatic breast cancer cells
  • critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation
  • genome-wide diurnal recruitment of HDAC3 directs a rhythm of epigenomic modification, Pol II recruitment, and gene expression
  • circadian NR1D1 recruitment of HDAC3 to lipid metabolic genes plays a critical physiological role
  • NR1D1 colocalizes with HDAC3 near genes regulating lipid metabolism
  • HDAC3 activity is necessary for osteoclast formation
  • essential role for HDAC3, a chromatin modifier, in hypoxia-induced epithelial-mesenchymal transition (EMT)
  • under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression
  • plays a critical and specific regulatory role in the neural crest-derived smooth muscle lineage and in formation of the cardiac outflow tract
  • IRF8, ETV6 and HDAC3 cooperated to increase sensitivity to FAS-induced apoptosis
  • HDAC3 exerted a negative regulation on expression of HDAC2 via interaction with RAC1
  • HDAC3 is involved in histone deacetylation of the IL12B promoter by IL10
  • central role in inflammation, providing use of selective HDAC inhibitors as antiinflammatory agents
  • nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression
  • its expression in osteoblasts and osteocytes is essential for bone maintenance during aging
  • is essential to the mechanism by which RUNX2 represses AXIN2
  • HDAC3 is able to regulate cyclin A degradation during mitosis via proteasome
  • plays a critical role in cardiac progenitor cells to regulate early cardiogenesis
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with nuclear receptor corepressor NCOR2
  • critical component of the N-CoR/SMRT repression complex
  • core repression complex involves the recruitment of three proteins, HDAC3, GPS2 and TBL1X, to a highly conserved repression domain within NCOR2 and NCOR
  • the formation of a stable and active HDAC3-corepressor complex is a stepwise process in which the C terminus of HDAC3 plays a critical role at late steps of the assembly process
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to YY1, involved in negative regulation of transcription
  • interacting with KLF6 (potential mechanism underlying human adipogenesis)
  • repressing DLK1
  • interacting with NCOR1 (functions as an activating subunit for the chromatin modifying enzyme histone deacetylase 3 (HDAC3)
  • interacting with SKI (SKI represses retinoic acid (RA) signaling by interacting with, and stabilizing, key components of the co-repressor complex, namely, HDAC3)
  • KIAA1967 is an endogenous inhibitor of HDAC3 (interacts and specifically inhibits the deacetylase HDAC3)
  • genomic recruitment of HDAC3 by NR1D1 directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis
  • EMD binds directly to HDAC3, the catalytic subunit of the nuclear co-repressor (NCoR) complex, and recruits HDAC3 to the nuclear periphery
  • HDAC3 mediates allergic skin inflammation in relation with angiogenesis by regulating MS4A2
  • HDAC3-RAC1 interaction, but not HDAC3 activity, is necessary for down-regulation of HDAC2 by RAC1
  • was necessary for the induction of CCL2
  • HDAC2, negatively regulated by MS4A2 and HDAC3, is under the control of proteasome-dependent ubiquitination
  • association of HDAC3 and HDAC6 with JDP2 and ATF3 occurs via direct protein-protein interactions
  • nuclear receptor co-repressors are required for HDAC3 enzyme activity in vivo and suggest that a deacetylase-independent function of HDAC3 may be required for life
  • RUNX2, HDAC3, repress AXIN2 transcription in osteoblasts
  • HDAC3 is necessary for ESR1 mRNA stability, and is involved in the estrogen-dependent proliferation of ESR1-positive tumors
  • HDAC3 directly interacts with and deacetylates CCNA2
  • HDAC3 regulates cyclin A stability by counteracting the action of the acetylases KAT2A/KAT2B
  • interaction with NCOR2 is essential for deacetylase-independent function of HDAC3
  • HDAC3 physically interacts with TBX5 and modulates its acetylation to repress TBX5-dependent activation of cardiomyocyte lineage-specific genes
  • RBM15 which associates with HDAC3 and the histone methyltransferase, SETD1B, binds to both MPL RNA and chromatin and regulates H4 acetylation and H3K4me3 marks
  • PDCD5 selectively mediates HDAC3 dissociation from TP53, which induces HDAC3 cleavage and ubiquitin-dependent proteasomal degradation
  • PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT1
  • interaction between NKAP and HDAC3 is critical for T Cell maturation
  • EMD regulation of HDAC3 activity to affect H4K5 acetylation dynamics is important for myogenic differentiation
  • HDAC3 interacts with FOXK1, co-localizes with FOXK1 at the promoter of STAT1 and STAT2, and is required for protecting FOXK1 from lysosomal system-mediated degradation
  • biological importance of HDAC3 in regulating the antiviral immunity of macrophages through interacting with FOXK1 to regulate the expression of STAT1 and STAT2
    • cell & other
    REGULATION
    induced by HIF1A (HDAC3is essential for hypoxia-induced EMT and metastatic phenotypes)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in squamous cell lung carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    blood  
    HDAC3 inhibitors are being considered as promising candidates for cancer therapy
    blood  
    promising target for therapies aiming to expand hematopoietic stem cells
    neurologyneurodegenerative 
    HDAC3 inhibitors being tested for relief of expansion-associated gene silencing may also suppress somatic expansions that contribute to disease progression
    allergy  
    HDAC3 serves as a target for development of allergy therapeutics.
    ANIMAL & CELL MODELS
  • deletion of Hdac3 or Nr1d1 in mouse liver causes hepatic steatosis