ATP-dependent chromatin remodeler CHD4

Function

ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Localizes to acetylated damaged chromatin in a ZMYND8-dependent manner, to promote transcriptional repression and double-strand break repair by homologous recombination. Involved in neurogenesis (By similarity).

Classification

Family (Pfam)

PF08074 CHDCT2, PF06461 CHDII_SANT-like, PF08073 CHDNT, PF00385 Chromo, PF06465 DUF1087, PF00271 Helicase_C, PF00628 PHD, PF00176 SNF2-rel_dom

InterPro

CHD_C2, CHD_II_SANT-like, CHD_N, Chromo-like_dom_sf, Chromo/chromo_shadow_dom, Chromo_domain, DNA/RNA_helicase_DEAH_CS, DUF1087, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, SNF2-like_sf, SNF2/RAD54-like_C, SNF2_N, Zinc_finger_PHD-type_CS, Znf_FYVE_PHD, Znf_PHD, Znf_PHD-finger, Znf_RING/FYVE/PHD

Functional cluster

DEAD-Box RNA Helicases & Biogenesis Factors

Experimental structures · PDB · 12

• 1MM2 NMR
• 1MM3 NMR
• 2EE1 NMR
• 2L5U NMR
• 2L75 NMR
• 2N5N NMR
• 4O9I X-ray 2.60A
• 6BGG NMR
• 6Q3M X-ray 2.52A
• 6RYR EM 3.10A
• 6RYU EM 4.00A
• 8D4Y X-ray 2.90A

A predicted model is available from AlphaFold.

Gene Ontology · 34

• GO:0005813 centrosome
• GO:0150048 cerebellar granule cell to Purkinje cell synapse
• GO:0000785 chromatin
• GO:0000781 chromosome, telomeric region
• GO:0005737 cytoplasm
• GO:0016020 membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0016581 NuRD complex
• GO:0032991 protein-containing complex
• GO:0090575 RNA polymerase II transcription regulator complex
• GO:0090734 site of DNA damage
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0140658 ATP-dependent chromatin remodeler activity
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0042393 histone binding
• GO:0042826 histone deacetylase binding
• GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
• GO:0001221 transcription coregulator binding
• GO:0003714 transcription corepressor activity
• GO:0008270 zinc ion binding
• GO:0006338 chromatin remodeling
• GO:0006351 DNA-templated transcription
• GO:0000724 double-strand break repair via homologous recombination
• GO:0045892 negative regulation of DNA-templated transcription
• GO:0010629 negative regulation of gene expression
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0042659 regulation of cell fate specification
• GO:2000736 regulation of stem cell differentiation
• GO:0051963 regulation of synapse assembly
• GO:0072553 terminal button organization

Disease associations

• Sifrim-Hitz-Weiss syndrome MONDO:0014946

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• ATP-dependent chromatin remodeler CHD4 1.00
• ATP-dependent chromatin remodeler CHD5 0.97
• ATP-dependent chromatin remodeler CHD5 0.97
• ATP-dependent chromatin remodeler CHD5 0.96
• ATP-dependent chromatin remodeler CHD3 0.93
• ATP-dependent chromatin remodeler Mi-2 0.87
• ATP-dependent chromatin remodeler chd-3 0.85
• Protein let-418 0.84
• ATP-dependent chromatin remodeler CHD6 0.77
• ATP-dependent chromatin remodeler CHD6 0.74
• ATP-dependent chromatin remodeler CHD6 0.74
• SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 homolog 0.73

Co-cited proteins · studied together in the literature

• Zinc finger CCCH-type with G patch domain-containing protein 1 shared papers
• ATP-dependent chromatin remodeler CHD3 5 shared papers
• Pericentrin 1 shared papers
• DNA-binding protein Ikaros 1 shared papers
• Histone-lysine N-methyltransferase NSD3 2 shared papers
• Zinc finger protein RFP 1 shared papers
• MYND-type zinc finger-containing chromatin reader ZMYND8 3 shared papers
• Histone deacetylase 1 6 shared papers
• Cyclin-dependent kinase 13 1 shared papers
• SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 2 shared papers
• Zinc finger protein 687 2 shared papers
• Metastasis-associated protein MTA3 4 shared papers

Literature · 41 cited papers

• ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation. Cell Death Dis. · 2022
• Cross-linking mass spectrometry reveals the structural topology of peripheral NuRD subunits relative to the core complex. FEBS J. · 2021
• Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations. Elife · 2020
• Positive Regulation of Transcription by Human ZMYND8 through Its Association with P-TEFb Complex. Cell Rep. · 2018
• The BRD3 ET domain recognizes a short peptide motif through a mechanism that is conserved across chromatin remodelers and transcriptional regulators. J. Biol. Chem. · 2018
• CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality. Nucleic Acids Res. · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage. Cell Rep. · 2016
• De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms. Am. J. Hum. Genet. · 2016
• Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat. Genet. · 2016
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
• … and 29 more in the literature graph