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FLASH GENE
Symbol HDAC1 contributors: mct/shn/ - updated : 06-11-2018
HGNC name histone deacetylase 1
HGNC id 4852
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , octamer , complex
HOMOLOGY
interspecies ortholog to hdac1, Danio rerio
ortholog to Hdac1, Rattus norvegicus
ortholog to Hdac1, Mus musculus
intraspecies homolog to HDAC2
Homologene
FAMILY
  • histone deacetylase/acuc/apha family
    • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    basic FUNCTION
  • histone deacetyltransferase, modulator of chromatin structure, repressor of gene expression putative mediator of the methylation process and regulation of gene transcription
  • down-regulates p53 function
  • required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation
  • controls myocardial growth, morphogenesis, and contractility
  • plays a central role in CYP1A1 expression and its removal is a necessary but not sufficient condition for CYP1A1 induction, underscoring the requirement for a concerted series of chromatin-remodeling events to complete the initial steps of gene trans-activation by the Ah receptor
  • controls neuronal development and required for neuronal specification
  • may repress CDKN1A and thus regulate cellular proliferation
  • implicated in the regulation of cell cycle progression by tumor suppressors, differentiation, cellular aging, and cancer
  • required for the controlled reprogramming of ES cells upon differentiation (unique requirement for HDAC1 in the optimal activity of HDAC1/2 corepressor complexes and cell fate determination during differentiation)
  • regulate unique and overlapping sets of genes in human erythroid progenitor cells
  • regulates p53-p21(Cip)-independent pathways critical for maintaining cell cycle progression
  • role in cell cycle regulation and haematopoiesis
  • HDAC1 and HDAC2 promote proper DNA double-strand break signaling and repair, predominantly through their requirement for effective NHEJ (nonhomologous end-joining)
  • HDAC1 and HDAC2 participate in the DNA-damage response through their recruitment to DNA damage (MID: 20802485)
  • crucial negative regulator of both SNAI1 and CDH1, and loss of HDAC1 cannot be compensated by upregulation of HDAC2, thereby showing a clear mechanistic difference in the two class I HDACs
  • critical for myelination of the peripheral nervous system (
  • controls Schwann cell survival by regulating the levels of active beta-catenin (
  • its overexpression decreased cell proliferation and cell division
  • has the ability to induce cellular senescence through deacetylated SP1 and the PPP2CA pathway
  • KDM1A and HDAC1 specify repressive chromatin marks in proinflammatory cytokines and classical complement pathway genes
  • is a key regulator of TP73 protein stability
  • HDAC1 and HDAC2 contribute differently to the development of specific hematopoietic lineages
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of a histone deacetylase complex containing HDAC2, AOF2, RCOR1, ZNF261, ZNF198, KIAA0182 and GTF2I
  • KAT5, UHRF1, HDAC1 and DNMT1 are present in the same macro-molecular complex and are partners for the epigenetic code inheritance
  • HDAC1 and HDAC2 interact together to form the catalytic core of a number of higher-order complexes including SIN3A, RCOR1
  • MEF2A/MEF2D dimers strongly interact with HDAC1, and to a lesser extent with HDAC7 in macrophages, whereas low levels of MEF2A/MEF2D–HDAC1 complexes are found in undifferentiated cells or in monocytes
  • complex containing the corepressor SIN3B, HDAC1, MORF4L1 and PHF12 plays important roles in regulation of transcription
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Sin3A-associated protein 130kDa, mSin3A
  • C-terminal binding protein 1, CTBP1
  • Sin3A-associated protein 30kDa, SAP30
  • CBF1/RBP-Jkappa
  • retinoblastoma-like 1 (p107) and retinoblastoma-like 2 (p130)
  • breast cancer 1, early onset, BRCA1
  • embryonic ectoderm development, EED
  • DNA (cytosine-5-)-methyltransferase 1, Dnmt1
  • histone deacetylase 9, HDAC9
  • retinoblastoma, Rb and retinoblastoma binding protein 4, RBBP4
  • HUS1 checkpoint homolog (S. pombe), HUS1 and RAD9 homolog A (S. pombe), RAD9A
  • BCL6 corepressor, BCoR
  • Receptor-interacting protein 140, RIP140
  • nuclear receptor corepressor 2, NCOR2
  • DNA topoisomerase II alpha and beta
  • REST corepressor 1, RCOR1
  • promyelocytic leukemia, PML
  • DNA (cytosine-5-)-methyltransferase 3 alpha, DNMT3A
  • TG-interacting factor 2, TGIF2
  • YY1 transcription factor, YY1
  • FK506 binding protein 3, 25kDa, FKBP25
  • protein ETO-2
  • EVI-1 and MDS1/EVI1
  • v-rel reticuloendotheliosis viral oncogene homolog A (avian), RELA
  • hairless homolog (mouse), HR
  • MyoD and pRb during skeletal myogenesis
  • heat shock 70kDa protein 4, HSPA4
  • suppressor of variegation 3-9 homolog 1 (Drosophila), SUV39H1
  • sal-like 1 (Drosophila), SALL1
  • PEX14 peroxisomal biogenesis factor 14, PEX14
  • Proliferating cell nuclear antigen, PCNA
  • NF-kappa B
  • inhibitor of growth family, member 1, ING1
  • androgen receptor, AR
  • Replication factor C, RFC
  • methyl-CpG binding domain protein 3, MBD3
  • tetradecanoyl phorbol acetate induced sequence 7, TIS7
  • bromodomain adjacent to zinc finger domain 2A, BAZ2A
  • myeloid translocation gene on chromosome 16 protein, MTG16
  • DNA (cytosine-5-)-methyltransferase 3-like, DNM3L and DNA (cytosine-5-)-methyltransferase 3 beta, DNMT3B
  • ERG-associated protein with SET domain, ESET
  • mesoderm induction early response 1 homolog alpha and beta, MIER1alpha and MIER1beta
  • EP300 interacting inhibitor of differentiation 2, EID2
  • EF-hand calcium binding domain 6, EFCAB6
  • Epstein-Barr virus (EBV) nuclear antigen 3C, EBNA3C
  • chromodomain helicase DNA binding protein 1, CHD1
  • protein inhibitor of activated STAT 4, PIAS4
  • metastasis associated 1, MTA1
  • chromodomain-Y-like, Cdyl
  • IkappaBalpha, IKBA
  • mortality factor 4 like 2, MORF4L2
  • estrogen receptor 1, ESR1
  • signal transducer and activator of transcription 1, STAT1 and signal transducer and activator of transcription 2, STAT2
  • APEX nuclease (multifunctional DNA repair enzyme) 1, APE1
  • transcription factor NF-E4, NFE4
  • p68 and p72 DEAD box RNA helicases
  • melanoma antigen family A, 1 (directs expression of antigen MZ2-E), MAGEA1
  • PHD finger protein 21A, PHF21A
  • B-cell CLL/lymphoma 3, BCL3
  • sucrose nonfermenting protein 2 homolog, SNF2h
  • EP300 interacting inhibitor of differentiation 3, EID3
  • regulatory factor X, 1 (influences HLA class II expression), RFX1
  • ethylmalonic encephalopathy 1, ETHE1
  • lysine-specific histone demethylase 1, LSD1
  • checkpoint with forkhead and ring finger domains, CHFR
  • peptidyl arginine deiminase type IV, PADI4
  • sphingosine-1-phosphate, S1P
  • FATS
  • interacting with EP300 and NR4A1 (acetylation of NR4A1 is modulated by EP300 and HDAC1, suggesting that acetylation is an important post-translational modification for the rapid turnover of NR4A1 protein)
  • SMARCAD1 modulates the interaction of HDAC1 and TRIM28 with heterochromatin
  • regulates synergistically with HDAC1 the expression of proinflammatory cytokines and genes of the classical complement pathway
  • FAM60A promotes the retention of HDAC1 but not SIN3A at the CCND1 promoter in asynchronously growing cells
  • HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes BHLHE40 sumoylation-dependent growth arrest
  • likely HDAC1 functionally interacts with BCOR during eye development and, along with BCL6, act together to mediate normal optic cup formation by preventing colobomata
  • TRPS1 interacts with two histone deacetylases, HDAC1 and HDAC4, thereby increasing their activity
  • HEXIM1 attenuated the interaction of HIF1A with HDAC1 (histone deacetylase 1), resulting in acetylation of HIF1A
  • HLCS acts as a biotin-independent transcriptional repressor interacting with HDAC1, HDAC2 and HDAC7
  • SIN3A-associated HDAC1/2-activity is essential for hematopoietic stem cell homeostasis
  • SETD6 associated with HDAC1 and MTA2
  • IKZF1 and HDAC1 regulate the epigenetic signature in leukemia, via regulation of KDM5B transcription
  • BRDT has novel interactions with the histone deacetylase HDAC1, the arginine-specific histone methyltransferase 5 PRMT5, and the Tripartite motif-containing 28 protein TRIM28, and functions in transcriptional repression during spermatogenesis
  • SLC6A4 is epigenetically downregulated by HDAC1 in several types of cancer
  • catalytic domain of TET3 interacts with HDAC1 and SIN3A, thus enhancing their binding to the IFNB1 promoter
  • PHF12 associates with a chromatin interacting protein complex comprised of MORF4L1, SIN3B, and HDAC1, that functions as a transcriptional modulator
  • RSF1 interacts with and recruits HDAC1 to centromeres
  • USP38 is involved in the DNA damage response (DDR) by regulating the activity of HDAC1
  • association of KCTD19 with zinc finger protein 541 (ZNF541) and histone deacetylase 1 (HDAC1)
    • cell & other
    REGULATION
    activated by PLAF
    inhibited by sphingosine-1-phosphate, S1P
    miR-449a in prostate cancer cells
    Other recruiting by MITR to downregulate MEF2 activity
    modified by SUMO-1 that modulates its biological activities
    deregulated by p25/Cdk5 induces aberrant cell-cycle activity and double-strand DNA breaks leading to neurotoxicity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    overexpressed in rheumatoid arthritis synovial fibroblasts (RA-SF), supporting cell proliferation and survival of RA-SF but suppressing MMP1 production
    constitutional        
    loss of HDAC1, but not HDAC2, reduces the level of HDAC activity associated with HDAC1/2 complexes and leads to the enhanced differentiation of embryoid bodies
    tumoral     --low  
    is linked to enhanced tumour malignancy
    constitutional     --over  
    led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (RB1) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PPP2CA)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker presence of HDAC1 could provide a biomarker for benign teratomas
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    induced premature senescence by HDAC1 overexpression may be a powerful tumor-suppressor mechanism for use in cancer therapy
    bloodhemoglobin 
    potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease
    ANIMAL & CELL MODELS
  • mice with conditional Hdac1 null alleles die by embryonic day 9.5
  • Cardiac-specific deletion of HDAC1 and HDAC2 genes results in neonatal lethality with cardiac arrhythmias, dilated cardiomyopathy, and up-regulation of genes encoding skeletal muscle-specific contractile proteins and calcium channels
  • deletion of both HDAC1 and HDAC2 genes in mouse developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7
  • ablation of Hdac1 and Hdac2 specifically in mouse Schwann cells, result in massive Schwann cell loss and virtual absence of myelin in mutant sciatic nerves (