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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
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