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FLASH GENE
Symbol CHD4 contributors: mct/shn - updated : 12-04-2019
HGNC name chromodomain helicase DNA binding protein 4
HGNC id 1919
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
39 - 6511 218 1912 - 2007 17626165
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumear     Mus musculus
Nervousbrain     Mus musculus
Urinary      Mus musculus
Visualeye     Mus musculus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral  highly Mus musculus
cell lineage highly expressed in thymocytes
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal tandem of PHD fingers (PHD1/2) linked by a stretch of 30 AAs, necessary for transcriptional repressive functions (PHD1 and PHD2) each contribute to the activity of CHD4, but PHD2 plays a more important role than PHD1) with tandem chromodomains in addition to centrally located ATPase/helicase domains
  • a nucleosome remodeling ATPase domain along with the two chromodomains
  • a central helicase: ATPase related SNF2 domain and a region with similarity to the Myb-DNA binding domain
  • SWI2/SNF2 ATPase/helicase domain of CHD4 is large (465 AAs) and complex, and ATPase domain with C terminus of CHD4 are necessary for the transcriptional repressive function of NuRD complexe
  • a pericentrin-binding domain
  • two domains of unknown function (DUFs)
  • C-terminal domain (CTD)
  • HOMOLOGY
    interspecies homolog to C.elegans f26f12.7
    ortholog to Chd4, Mus musculus
    ortholog to Chd4, Rattus norvegicus
    ortholog to CHD4, Pan troglodytes
    intraspecies paralog to CHD2, CHD7, CHD8
    Homologene
    FAMILY SNF2/RAD54 helicase family
    CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome
    text
  • is a core component of the nucleosome remodeling and deacetylase (NuRD) complex, which possesses both chromatin remodeling and histone deacetylation activities
  • basic FUNCTION
  • involved in transcriptional repression in the nucleus, co-localize with MCRS1 in the nucleolus and appear to activate the rRNA transcription
  • required at several steps during T cell development: for differentiation of beta selected immature thymocytes, for developmental expression of CD4, and for cell divisions in mature T cells
  • novel functions for CHD4 in the DNA-damage response (DDR) and cell-cycle control
  • acts as an important regulator of the G1/S cell-cycle transition by controlling TP53 deacetylation
  • an important role of CHD4 in controlling homologous recombination repair to maintain genome stability
  • SMARCA4 and CHD4 antagonistically modulate Wnt signaling in developing yolk sac vessels to mediate normal vascular remodeling
  • ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression
  • is not only a chromatin remodeler but also a critical subunit of a multiprotein histone deacetylase complex, suggesting that alteration in chromatin modeling and histone acetylation may be the culprit
  • CELLULAR PROCESS nucleotide, chromatin organization, remodeling
    nucleotide, repair
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • core component of the NURD complex
  • ATP dependent chromatin remodeler and a major subunit of the repressive NURD complex
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • HDAC1/2
  • Ataxia telangiectasia mutated (ATM)- and Rad3-related protein, ATR
  • Ikaros
  • BRG1 and RET finger protein
  • RORgamma
  • microspherule protein1, MCRS1
  • c-MYC
  • Pericentrin
  • DJ-1
  • TWIST protein complex
  • ATM kinase
  • could bind to two H3 N-terminal tails on the same nucleosome or on two separate nucleosomes simultaneously, presenting exciting implications for the mechanism by which CHD4 and the NuRD complex could direct chromatin remodeling
  • BRD4
  • CBX1 and CBX3
  • BRIT1
  • histone binding by the CHD4 PHD1/2 fingers is required for transcriptional repressive activity of the CHD4/NURD complex, supporting the mechanism of multivalent engagement
  • CHD4/NuRD maintains demethylation state of rDNA promoters through inhibiting the expression of the rDNA methyltransferase recruiter BAZ2A
  • ZFHX4 interacts with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex
  • genes commonly regulated by both KDM5A and CHD4 were categorized as developmentally regulated genes
  • CHD4 is a transcriptional regulator of PLS3
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SIHIWES
    Susceptibility
  • to dermatomyositis
  • to Chiari I malformation (CM1)
  • Variant & Polymorphism other
  • de novo mutations in CHD4 among individuals with CM1
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • CHD4 deficiency impairs the recruitment of DNA repair proteins BRIT1, BRCA1, and replication protein A at early steps of homologous recombination repair
  • null Chd4 mouse embryos cannot complete the first lineage step at the blastocyst stage