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FLASH GENE
Symbol HDAC1 contributors: mct/shn/ - updated : 06-11-2018
HGNC name histone deacetylase 1
HGNC id 4852
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon highly
 mouthtongue  highly
 stomach   highly
Reproductivefemale systembreastmammary gland highly
cell lineage
cell lines
fluid/secretion
at STAGE
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 (