Affinage

CHD4

ATP-dependent chromatin remodeler CHD4 · UniProt Q14839

Length
1912 aa
Mass
218.0 kDa
Annotated
2026-04-28
100 papers in source corpus 58 papers cited in narrative 58 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHD4 is an ATP-dependent chromatin remodeling ATPase that serves as the catalytic engine of the NuRD complex and the ChAHP complex, repositioning nucleosomes to regulate transcription, DNA damage repair, and genome architecture across diverse cell types. Its tandem PHD fingers bivalently engage two histone H3 tails on a single nucleosome in a modification-sensitive manner, while intramolecular auto-inhibition by a C-terminal SANT-SLIDE domain and RNA-mediated competition for nucleosome binding tune its remodeling output; cryo-EM and single-molecule studies show the ATPase motor distorts DNA at superhelical location SHL+2 and drives a decoupled entry/exit translocation mechanism (PMID:32543371, PMID:32251276, PMID:22575888, PMID:36473839, PMID:35649367). CHD4 is rapidly recruited to DNA double-strand breaks in a PAR- and ATM-dependent manner, where it promotes chromatin relaxation, HP1 displacement, and homologous recombination repair (PMID:20693977, PMID:20805324, PMID:31970415, PMID:22219182). Through interactions with lineage-specific transcription factors (GATA4, NKX2-5, TBX5, GATA3, PAX3-FOXO1) and lncRNAs, CHD4 represses lineage-inappropriate gene programs to maintain cell identity in the heart, skeletal muscle, neurons, thymic epithelium, and lymphocytes; de novo CHD4 missense mutations cause Sifrim-Hitz-Weiss syndrome with variant-specific alterations in ATPase and remodeling activities (PMID:27166947, PMID:35450884, PMID:32647123, PMID:32601470, PMID:31388190, PMID:37254794).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 Medium

    Establishing that CHD4 physically associates with DNA-damage-signaling kinases: ATR was found to co-purify with CHD4 and HDAC2, linking the NuRD complex to the DNA damage checkpoint machinery for the first time.

    Evidence Tandem MS purification followed by reciprocal co-IP from human cell extracts

    PMID:10545197

    Open questions at the time
    • Functional consequence of ATR–CHD4 interaction was not tested
    • No in vivo validation
    • Directness of the ATR–CHD4 contact versus bridging through other NuRD subunits was not resolved
  2. 2007 High

    Demonstrating that CHD4 directly represses specific developmental genes in vivo: gain- and loss-of-function in Xenopus showed CHD4 binds the Sip1 locus and controls neuroectoderm/mesoderm boundary specification through Nodal signaling epistasis.

    Evidence CHD4 ChIP at Sip1 gene body plus genetic epistasis in Xenopus embryos

    PMID:17438000

    Open questions at the time
    • Mechanism of CHD4 targeting to the Sip1 locus unknown
    • Whether NuRD or an alternative CHD4 complex mediates this function was not tested
  3. 2009 High

    Defining the histone-reading code of CHD4's PHD fingers: PHD2 was shown to read the H3 N-terminus with selectivity enhanced by H3K9 acetylation/methylation and inhibited by H3K4 methylation, establishing how chromatin marks direct CHD4 recruitment.

    Evidence NMR, tryptophan fluorescence, and peptide binding assays with quantitative affinities

    PMID:19624289

    Open questions at the time
    • PHD1 contribution was not yet characterized
    • Nucleosomal context not tested in this study
  4. 2010 High

    Establishing CHD4 as a rapid responder to DNA double-strand breaks: two independent studies showed PAR-dependent recruitment of CHD4/NuRD to damage sites, ATM-dependent CHD4 phosphorylation, and that CHD4 loss impairs the RNF168-ubiquitin-BRCA1 cascade and the G1/S checkpoint.

    Evidence Laser micro-irradiation, siRNA knockdown, FRAP, co-IP, cell cycle analysis, clonogenic survival in human cells

    PMID:20693977 PMID:20805324

    Open questions at the time
    • Direct biochemical mechanism of PAR-dependent recruitment not yet resolved
    • Whether CHD4 remodeling activity per se is required at DSBs was unclear
  5. 2011 High

    Resolving both PHD fingers as bivalent H3-tail readers and showing ATM phosphorylation regulates CHD4 chromatin retention: structural and phospho-mutant analyses demonstrated that both PHD1 and PHD2 bind H3, and that ATM-mediated phosphorylation enhances CHD4 chromatin association after DNA damage.

    Evidence NMR structure of PHD2–H3K9me3 complex; phospho-mutant overexpression with chromatin fractionation and comet assay

    PMID:21219611 PMID:21278251

    Open questions at the time
    • Whether bivalent PHD engagement occurs on one nucleosome or across nucleosomes was unresolved
    • Specific ATM phosphosites in CHD4 were not fully mapped
  6. 2012 High

    Establishing the intramolecular regulatory architecture and multivalent nucleosome engagement of CHD4: SAXS models revealed extensive PHD–chromo–motor interdomain contacts that allosterically regulate ATPase activity, and bivalent PHD binding to two H3 tails on a single nucleosome was shown to displace HP1γ and be required for NuRD repressive function. CHD4 was also linked to BRIT1-dependent homologous recombination.

    Evidence SAXS structural modeling, ATPase/remodeling assays with domain deletions, nucleosome binding assays, DR-GFP HR reporter, PARP inhibitor sensitivity

    PMID:22215588 PMID:22219182 PMID:22575888 PMID:22749909 PMID:23071088

    Open questions at the time
    • No atomic-resolution structure of full-length CHD4 or its nucleosome complex
    • Whether auto-inhibition involves the C-terminal region was not yet known
  7. 2013 High

    Defining CHD4 as a cell-identity guardian in multiple tissues: studies showed CHD4 partners with GATA3 in dual activation/repression complexes in Th2 cells, cooperates with Ezh2/PRC2 to repress astrogenic genes in the developing cortex, controls vascular integrity by repressing uPAR/thrombospondin in endothelial cells, maintains rDNA promoter methylation states, and acts as a RanGTP-dependent mitotic spindle MAP.

    Evidence Tissue-specific conditional KO mice (endothelium), Co-IP/ChIP in Th2 cells and neural progenitors, in utero electroporation, Xenopus egg extract immunodepletion, bisulfite sequencing of rDNA

    PMID:23471993 PMID:23624931 PMID:23796711 PMID:24268414 PMID:24348274

    Open questions at the time
    • Mechanism of CHD4's chromatin-independent spindle function not biochemically defined
    • How CHD4 switches between activation and repression complexes in the same cell was unclear
  8. 2015 High

    Identifying the N-terminal HMG-like domain as a PAR-binding module required for DNA damage recruitment and full remodeling: NMR structure of CHD4-N showed structural similarity to HMG boxes and demonstrated higher affinity for PAR than for DNA.

    Evidence NMR structure determination, PAR-binding assay, nucleosome remodeling assay, laser micro-irradiation

    PMID:26565020

    Open questions at the time
    • Whether PAR binding is the sole recruitment mechanism was debated
    • Contribution of the N-terminal domain to NuRD versus ChAHP function was not tested
  9. 2016 High

    Demonstrating CHD4 modularity within NuRD and its role in maintaining striated muscle identity: biochemical reconstitution showed CHD4 is a peripheral NuRD component whose addition restores remodeling to a core HDAC sub-complex; cardiac- and skeletal-muscle-specific CHD4 knockouts revealed cross-expression of inappropriate sarcomere programs causing cardiomyopathy.

    Evidence In vitro NuRD reconstitution with activity assays; tissue-specific conditional KO mice with echocardiography and transcriptomics

    PMID:27166947 PMID:27235397 PMID:27760049

    Open questions at the time
    • How CHD4 is peripherally recruited to the NuRD core was structurally undefined
    • Whether CHD3-NuRD can compensate in CHD4-null muscle was not tested
  10. 2018 High

    Discovering RNA-mediated regulation and the ChAHP complex: ADNP–CHD4–HP1 forms a stable ChAHP complex that represses lineage genes independently of H3K9me3; the lncRNA PAPAS guides CHD4/NuRD to rDNA via dephosphorylation-enhanced RNA binding; PAR-dependent but non-PAR-binding recruitment to DNA breaks was clarified as requiring prior PARP1/Alc1-mediated chromatin relaxation.

    Evidence Co-IP/MS, ChIP-seq/ATAC-seq in mESCs, RIP with domain mapping, phosphorylation analysis, live-cell fluorescence three-hybrid and FRAP at laser damage sites

    PMID:29733391 PMID:29795351 PMID:29891665 PMID:29907651

    Open questions at the time
    • Structural basis of ChAHP assembly unknown
    • Whether RNA regulation applies genome-wide beyond rDNA was not established
    • How dephosphorylation is coordinated with stress signaling was not fully resolved
  11. 2019 High

    Linking CHD4 disease mutations to quantitative enzymatic defects: Sifrim-Hitz-Weiss syndrome missense variants across different domains were shown to alter ATP hydrolysis and remodeling in variant-specific ways, establishing a genotype–enzymology correlation.

    Evidence In vitro ATPase and nucleosome remodeling assays on purified recombinant variant proteins

    PMID:31388190

    Open questions at the time
    • Cellular and developmental consequences of each variant not tested
    • No structural explanation for variant-specific kinetic changes
  12. 2020 High

    Solving the mechanism of nucleosome remodeling at atomic and single-molecule resolution and defining CHD4's role in genome architecture: cryo-EM at 3.1 Å revealed CHD4's ATPase motor at SHL+2 introducing a twist defect without terminal DNA unwrapping; single-molecule FRET demonstrated decoupled entry/exit translocation. Genome-wide studies showed CHD4 controls chromatin accessibility, cohesin distribution, and 3D genome organization in neurons and thymic epithelium. SIRT6 was identified as an upstream recruiter of CHD4 to DSBs for HP1 displacement. ZNF410 was identified as a dedicated transcriptional activator of CHD4 itself in erythroid cells.

    Evidence Cryo-EM structure, single-molecule FRET/force-extension, conditional KO with Hi-C/ATAC-seq/ChIP-seq in neurons and thymic epithelium, Co-IP at damage sites, CRISPR screen and crystallography for ZNF410

    PMID:31970415 PMID:32251276 PMID:32543371 PMID:32601470 PMID:32647123 PMID:33301730

    Open questions at the time
    • No structure of CHD4 within the full NuRD complex on a nucleosome
    • How decoupled translocation relates to nucleosome sliding direction in vivo is unknown
    • Whether ZNF410-CHD4 regulatory axis operates outside erythroid lineage was not tested
  13. 2022 High

    Revealing auto-inhibition, RNA competition, and transcription-factor-directed genomic targeting: the C-terminal SANT-SLIDE domain was shown to auto-inhibit the helicase domain until substrate DNA engagement; RNA was found to globally inhibit CHD4 nucleosome remodeling by competing with the substrate via two IDRs; cardiac TFs GATA4/NKX2-5/TBX5 recruit CHD4 to silencer elements whose deletion causes sarcomere gene misexpression; and CHD4 functions as a chromatin proofreader concealing cryptic CTCF sites in heterochromatin.

    Evidence In vitro domain-deletion remodeling assays, single-molecule assays, iCLIP, IP-MS in embryonic hearts, CRISPR deletion of silencer elements in vivo, Hi-C/ATAC-seq in CHD4-depleted cells

    PMID:34764232 PMID:35450884 PMID:35649367 PMID:36473839

    Open questions at the time
    • Structural basis of auto-inhibition relief upon nucleosome engagement not solved
    • Identity and stoichiometry of inhibitory RNAs in vivo not defined
    • How CHD4 distinguishes legitimate from cryptic CTCF sites mechanistically is unclear
  14. 2024 High

    Extending CHD4's role to chromatin proofreading and metabolic regulation: CHD4 was shown to position nucleosomes over GATA3 binding motifs to prevent inappropriate TF access during reprogramming; CHD4 interacts with SMYD1 to co-repress glycolytic and hypoxia-response genes in the developing heart; and FBXW7-mediated ubiquitin-proteasome degradation was identified as a regulatory mechanism controlling CHD4 protein levels.

    Evidence MNase-seq/ATAC-seq/ChIP-seq for nucleosome positioning, IP-MS with parallel conditional KO transcriptomics, ubiquitination assay and protein stability analysis

    PMID:38268032 PMID:38281186 PMID:38619323

    Open questions at the time
    • Whether chromatin proofreading is a general CHD4 function beyond GATA3 contexts is untested
    • FBXW7-CHD4 degradation axis not confirmed in non-cancer settings
    • How SMYD1 methyltransferase activity cooperates with CHD4 remodeling mechanistically is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structure of CHD4 within an intact NuRD complex engaged with a nucleosome; how CHD4 is switched between transcriptional activation and repression modes at the same locus; the in vivo identity and regulatory logic of inhibitory RNAs; and the full spectrum of developmental consequences of individual Sifrim-Hitz-Weiss syndrome variants.
  • No structure of CHD4 within holo-NuRD on a nucleosome substrate
  • Mechanism distinguishing activation from repression at shared loci is unknown
  • In vivo functional characterization of individual SHWS variants in animal models is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 6 GO:0003677 DNA binding 4 GO:0042393 histone binding 3 GO:0003723 RNA binding 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005634 nucleus 6 GO:0005694 chromosome 5 GO:0005856 cytoskeleton 1
Pathway
R-HSA-4839726 Chromatin organization 8 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-73894 DNA Repair 6 R-HSA-1266738 Developmental Biology 5 R-HSA-1640170 Cell Cycle 3
Partners
ADNPGATA3GATA4NKX2-5SIRT6SMYD1TBX5ZNF410
Complex memberships
ChAHPNuRD

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 CHD4 mediates rapid poly(ADP-ribose)-dependent recruitment of the NuRD complex to DNA-damage sites and is a phosphorylation target for the ATM kinase after DNA damage. CHD4 promotes repair of DNA double-strand breaks and acts as a regulator of the G1/S cell-cycle transition by controlling p53 deacetylation. siRNA knockdown, laser micro-irradiation/IRIF, co-IP, immunofluorescence, cell cycle analysis The EMBO journal High 20693977
2010 CHD4 becomes transiently immobilized on chromatin after ionizing radiation; its depletion triggers enhanced Cdc25A degradation and p21 accumulation, more pronounced CDK inhibition, and disrupts the chromatin response at the level of the RNF168 ubiquitin ligase, impairing local ubiquitylation and BRCA1 assembly at DSBs. Mass spectrometry screen for chromatin-immobilized proteins after IR, siRNA knockdown, FRAP, immunofluorescence, clonogenic survival The Journal of cell biology High 20805324
1999 ATR physically associates with CHD4 (Mi-2β) and HDAC2 as identified by tandem mass spectrometry purification; endogenous ATR, CHD4, and HDAC2 co-immunoprecipitate, and other NuRD members (HDAC1, MTA1, MTA2) are also detectable in ATR immunoprecipitates. Biochemical purification followed by tandem MS sequencing, co-immunoprecipitation, co-elution through two purification steps Biochemistry Medium 10545197
2009 The second PHD finger (PHD2) of CHD4 recognizes the N-terminus of histone H3; binding is facilitated by H3K9 acetylation or methylation (affinity rises to 0.6 µM for H3K9ac) but inhibited by H3K4 methylation (affinity drops to 2.0 mM for H3K4me3) or H3A1 acetylation. Phosphorylation of H3 Thr3, Thr6, or Ser10 abolishes the interaction. Tryptophan fluorescence, NMR, peptide library screen, mutagenesis, data-driven docking The Biochemical journal High 19624289
2011 The two PHD fingers (PHD1 and PHD2) of CHD4 both bind the N-terminus of histone H3; PHD2 uses a cation-π recognition mechanism for methylated K9. Solution structure of PHD2 in complex with H3K9me3 was determined by NMR. NMR structure determination, fluorescence binding assays, peptide binding experiments The Journal of biological chemistry High 21278251
2012 The tandem PHD1/2 fingers of CHD4 target nucleosomes in a multivalent manner by concomitantly engaging two histone H3 tails; this synergistic bivalent interaction displaces HP1γ from pericentric sites, induces changes in chromatin structure, and disperses H3K9me3. PHD finger–H3 recognition is required for repressive activity of the CHD4/NuRD complex. Fluorescence binding assays, nucleosome binding, co-immunoprecipitation, chromatin fractionation, cell-based repression assays with PHD mutants Proceedings of the National Academy of Sciences of the United States of America High 22215588
2012 The PHD and chromo domains of CHD4 regulate its ATPase activity through intramolecular allosteric interactions. SAXS-based three-dimensional structural model reveals extensive domain–domain contacts that regulate chromatin remodeling. Small-angle X-ray scattering (SAXS), ATPase assays, nucleosome remodeling assays, limited proteolysis, crosslinking mass spectrometry Journal of molecular biology High 22575888
2012 Concerted action of the PHD, chromo and motor domains allosterically regulates DNA binding, histone binding, and ATPase activities of CHD4; SAXS molecular shape reconstruction reveals extensive interdomain interactions. SAXS, domain-deletion constructs, ATPase and DNA binding assays FEBS letters High 22749909
2012 CHD4 is a novel BRIT1 (MCPH1) binding partner; BRCA1 C-terminal domains of BRIT1 are required for its interaction with CHD4. Depletion of CHD4 impairs BRIT1 recruitment to DNA damage sites, reduces BRCA1 recruitment, and impairs homologous recombination repair efficiency. CHD4-deficient cells are sensitized to PARP inhibitors. Co-IP, siRNA knockdown, HR reporter (DR-GFP), immunofluorescence, PARP inhibitor sensitivity assays The Journal of biological chemistry High 22219182
2011 ATM phosphorylates CHD4 in response to ionizing radiation; this phosphorylation affects CHD4's intranuclear organization by increasing chromatin binding/retention. Cells overexpressing a phospho-mutant CHD4 (unable to be phosphorylated by ATM) fail to show enhanced chromatin retention after DSBs and display high rates of spontaneous damage. Phospho-mutant overexpression, immunofluorescence, chromatin fractionation, comet assay Genome integrity Medium 21219611
2006 NAB2 represses transcription through a domain that uniquely requires interaction with CHD4 (a NuRD subunit). Both NAB1 and NAB2 can bind CHD3 or CHD4; NAB2–CHD4 interaction regulates the Rad promoter in myelinating Schwann cells; alternative splicing of NAB2 mRNA regulates its interaction with CHD4. Co-IP, chromatin immunoprecipitation (ChIP), reporter repression assays, siRNA The Journal of biological chemistry High 16574654
2013 CHD4 is a RanGTP-dependent microtubule-associated protein (MAP); it localizes to the mitotic spindle, stabilizes microtubules, and is required for bipolar spindle formation. Immunodepletion from Xenopus egg extracts reduces MT production around chromatin and prevents spindle assembly. This function is independent of chromatin remodeling. Immunodepletion from Xenopus egg extracts, RNAi in HeLa and Drosophila S2 cells, spindle assembly assay, live imaging Current biology : CB High 24268414
2015 The N-terminal region of CHD4 contains a domain (CHD4-N) with structural similarity to the HMG box that binds poly(ADP-ribose) with higher affinity than DNA; this N-terminal region (though not CHD4-N alone) is essential for full nucleosome remodeling activity and for localizing CHD4 to DNA damage sites. NMR structure determination, PAR-binding assay, nucleosome remodeling assay, laser micro-irradiation/IRIF The Journal of biological chemistry High 26565020
2016 CHD4 is a peripheral rather than central component of the NuRD complex. A stable NuRD sub-complex lacking CHD4 retains HDAC activity; addition of recombinant CHD4 reconstitutes full nucleosome remodeling activity. Biochemical reconstitution, HDAC activity assay, nucleosome remodeling assay The Journal of biological chemistry High 27235397
2017 CHD3 and CHD4 form distinct, isoform-specific NuRD complexes (not co-existing in the same complex); both associate with HP1 and rapidly accumulate at UV-induced DNA repair sites, but CHD3 and CHD4 show distinct nuclear localization patterns and exhibit different nucleosome remodeling and positioning behaviors in vitro. Immunoprecipitation/MS, in vitro nucleosome remodeling assay, FRAP, live-cell imaging Nucleic acids research High 28977666
2018 ADNP interacts with CHD4 and HP1 to form a stable ternary ChAHP complex; ADNP mediates complex assembly and recognizes DNA motifs for euchromatic binding. ChAHP represses lineage-specifying genes by establishing inaccessible chromatin locally, independently of H3K9me3. ADNP nonsense mutations disrupt complex integrity. Co-IP, mass spectrometry, ChIP-seq, ATAC-seq, genetic knockout in mESCs Nature High 29795351
2018 PAPAS lncRNA forms a DNA-RNA triplex tethering it to the rDNA enhancer; the N-terminal region of CHD4 interacts directly with an unstructured A-rich region in PAPAS to guide CHD4/NuRD to the rDNA promoter. Stress-induced dephosphorylation of CHD4 at three serine residues enhances CHD4/NuRD–RNA interaction and reinforces rDNA transcriptional repression. Protein-RNA interaction (RIP), RNA secondary structure mapping, deletion/mutation analysis, phosphorylation analysis, rRNA synthesis assay Genes & development High 29907651
2018 CHD4 depletion induces global chromatin relaxation in AML cells. Sensitization to daunorubicin and ara-C is mediated partly by Tip60-dependent ATM pathway activation in response to chromatin relaxation, followed by further ATM activation by DSBs. CHD4 is also necessary for tumor-forming behavior of AML cells. shRNA knockdown, chromatin accessibility assay, xenograft mouse model, clonogenic and colony assays Blood Medium 26265695
2013 CHD4 is an interaction partner of Ezh2 (PRC2) required specifically for PcG-mediated suppression of the astrogenic gene GFAP. In vivo depletion of Chd4 in the developing neocortex promotes premature astrogenesis. Co-IP, in utero electroporation knockdown, immunofluorescence, gene expression analysis The EMBO journal Medium 23624931
2013 Gata3 forms two functionally distinct complexes with Chd4 in Th2 cells: a Gata3/Chd4/p300 transcriptional activation complex at Th2 cytokine loci and a Gata3/Chd4-NuRD repression complex at the Tbx21 locus. Both complexes are required for Th2 cell identity and in vivo Th2-dependent inflammation. Co-IP, ChIP, gene expression analysis, in vivo asthma model Proceedings of the National Academy of Sciences of the United States of America High 23471993
2013 CHD4 directly controls transcription of uPAR (Plaur) and thrombospondin-1 (Thbs1) in endothelial cells by binding their promoters (shown by ChIP), thereby regulating plasmin activation. Endothelial-specific deletion of Chd4 causes embryonic vascular rupture due to excessive ECM proteolysis. Conditional knockout mouse, ChIP, qPCR array, plasmin activity assay, genetic rescue (urokinase reduction) PLoS genetics High 24348274
2012 Repressive activity of NuRD complexes requires the two chromodomains and ATPase/helicase and C-terminal domains (CTD) of CHD4, and the presence of MBD2 binding methylated DNA. Loss of MBD2 expression or DNA methylation impairs CHD4 association with the mb-1 promoter chromatin. CHD4 domain-deletion constructs in B cell reporter system, ChIP, transcription assays Molecular and cellular biology Medium 23071088
2015 p300 and CHD4 are both recruited to DSBs and physically interact; this interaction requires the chromodomain and ATPase/helicase domain of CHD4 and the CH2, Bd and HAT domains of p300. Each promotes the other's recruitment, and their co-operation is required for HR repair (not NHEJ) and RPA loading. Co-IP, purified protein pull-down, DR-GFP/EJ5-GFP reporter assays, immunofluorescence Mutagenesis Medium 26546801
2016 ZFHX4 interacts with CHD4 (a core NuRD member); ZFHX4 and CHD4 bind overlapping genomic loci and control similar gene expression programs in GBM tumor-initiating cells. ZFHX4 acts as a master regulator of CHD4 activity to maintain the tumor-initiating cell state. Co-IP, ChIP-seq, gene expression analysis, shRNA screen, intracranial xenograft Cell reports Medium 24440720
2016 Loss of CHD4 in the heart triggers aberrant expression of the skeletal muscle gene program, causing severe cardiomyopathy. Loss in skeletal muscle causes inappropriate cardiac gene expression and myopathy. Chd4/NuRD is required for maintaining striated muscle identity and mitochondrial function. Cardiac/skeletal muscle-specific conditional Chd4 knockout mice, echocardiography, gene expression, histology Cell metabolism High 27166947
2016 CHD4 interacts with the oncogenic fusion protein PAX3-FOXO1 via short DNA fragments; together they bind regulatory regions of PAX3-FOXO1 target genes. CHD4 depletion reduces viability of fusion-positive but not fusion-negative RMS cells and causes specific regression of fusion-positive xenografts. IP/MS interactome, ChIP-seq, gene expression analysis, shRNA knockdown, xenograft The Journal of clinical investigation High 27760049
2017 CHD4 recruits repressive chromatin proteins including DNA methyltransferases to sites of DNA damage repair (including oxidative lesions via OGG1 and DSBs via ZMYND8), imposes de novo DNA methylation, and its retention at tumor suppressor genes maintains their silencing in colorectal cancer. Co-IP, ChIP, bisulfite sequencing, CHD4 knockdown with gene reactivation assay Cancer cell Medium 28486105
2018 CHD4 and NuRD directly bind promoters of cardiac sarcomere-related genes (smooth muscle myosin heavy chain, fast skeletal α-actin, fast skeletal troponin complex) to repress noncardiac myofibril isoforms; loss of CHD4 causes cardiomyocytes to form hybrid muscle cells that disrupt sarcomere formation. Conditional cardiac CHD4 knockout, RNA-seq, ChIP-seq, genome-wide CHD4 occupancy, histology, cardiac function assessment Proceedings of the National Academy of Sciences of the United States of America High 29891665
2018 CHD4 depletion increases H2A.Z-dependent protein stability (H2A.Z stabilizes CHD4 by inhibiting proteasome-mediated degradation). CHD4 represses Tbx3 transcription in ESCs; the Chd4–Tbx3 axis controls ESC fate. CHD4 also interacts with H2A.Z. Co-IP, RNAi, CRISPR KO rescue experiments, gene expression profiling, protein stability assay The Journal of biological chemistry Medium 28298436
2018 Neutralizing the Gatad2a-Chd4-Mbd3 axis within Mbd3/NuRD blocks reestablishment of naive pluripotency; Gatad2a deletion specifically disrupts Mbd3/NuRD repressive activity on pluripotency circuitry without ablating somatic cell proliferation. Post-translational modifications of Mbd3/NuRD influence its interactions and assembly. CRISPR/gene deletion in mESCs, iPSC reprogramming assays, mass spectrometry analysis of complex composition Cell stem cell Medium 30122475
2020 Cryo-EM structure of human CHD4 engaged with a nucleosome (3.1 Å resolution) shows the ATPase motor binds and distorts nucleosomal DNA at superhelical location SHL+2, supporting the 'twist defect' model. Unlike Chd1, CHD4 does not induce unwrapping of terminal DNA. The structure maps cancer- and Sifrim-Hitz-Weiss syndrome-associated CHD4 mutations. Cryo-electron microscopy structure determination eLife High 32543371
2020 Single-molecule assays reveal that CHD4 binding energy (even without nucleotide) triggers significant conformational changes in DNA at the entry side; during remodeling, entry-side DNA moves continuously/gradually while exit-side DNA exits in concerted 4–6 bp steps. This decoupled translocation suggests ATP-driven entry-side strain released by DNA expulsion at the exit side. Single-molecule FRET and force-extension assays Nature communications High 32251276
2020 ZNF410 directly activates transcription of CHD4 in erythroid cells via two highly conserved, genomically unique clusters of ZNF410 binding sites near the CHD4 gene; loss of ZNF410 reduces CHD4 levels by ~60% and de-represses fetal hemoglobin genes. Crystal structure of ZNF410 bound to its DNA motif was determined. CRISPR-Cas9 screen, crystallography, ChIP-seq, luciferase reporter, xenotransplantation Molecular cell High 33301730
2020 SIRT6 translocates to DNA damage sites where it interacts with and recruits CHD4; CHD4 then displaces HP1 from H3K9me3 to promote chromatin relaxation and HR repair. Loss of either SIRT6 or CHD4 impairs chromatin relaxation, disrupts HR, and sensitizes cancer cells to DNA damaging agents. This process is ATM-dependent. Co-IP, immunofluorescence at DNA damage sites, chromatin accessibility assay, HR assay, conditional KO Nucleic acids research High 31970415
2020 CHD4 physically interacts with HIF1α and HIF2α subunits; under normoxia, CHD4 enrichment at HIF target gene promoters increases RNA polymerase II loading through p300. Hypoxia promotes CHD4 chromatin binding via HIF1/2α, and CHD4 enhances HIF1α recruitment. Co-IP, ChIP, gene expression analysis, mouse xenograft, loss-of-function rescue Cancer research Medium 32699137
2020 Conditional knockout of Chd4 in cerebellar granule neurons increases genome-wide chromatin accessibility, promotes cohesin recruitment preferentially to gene enhancers, and strengthens interactions among repressed contact domains and genomic loops, demonstrating that CHD4 controls genome architecture in the brain. Conditional KO mouse, ATAC-seq, ChIP-seq, Hi-C genome architecture profiling Nature communications High 32647123
2020 Chd4 organizes promoter regions of Fezf2-dependent self-antigen genes in medullary thymic epithelial cells and contributes to Aire-mediated self-antigen induction via super-enhancers, thereby coordinating central immune tolerance. Chd4 conditional KO in thymic epithelium causes autoimmune phenotypes. Conditional KO mouse, ChIP-seq, RNA-seq, immunohistochemistry Nature immunology High 32601470
2018 CHD3 and CHD4 are recruited to DNA damage sites in a PAR-dependent but PAR-non-binding manner; early PAR-dependent chromatin relaxation by PARP1/Alc1 is required to facilitate their subsequent recruitment via DNA binding. Both CHD3 and CHD4 actively contribute to chromatin remodeling at DNA breaks. Live-cell fluorescence three-hybrid assay, FRAP, laser micro-irradiation, PARP inhibitor treatment Nucleic acids research High 29733391
2019 CHD4 mutations (R975H, R1162W) found in endometrial cancer reduce CHD4 protein stability without impairing NuRD complex formation or DNA recruitment, phenocopying CHD4 depletion. CHD4 depletion induces cancer stem cell markers via TGF-β signaling pathway activation. Gene engineering (mutation knock-in), protein stability assays, Co-IP for NuRD complex, TGF-β inhibition rescue, in vivo tumor assays American journal of cancer research Medium 29888111
2019 CHD4 variants associated with Sifrim-Hitz-Weiss syndrome alter ATP hydrolysis and nucleosome remodeling activities in a variant-specific manner. Missense substitutions in different protein domains (SNF2-like, PHD, chromo) each produce measurable changes in CHD4 catalytic function. ATP hydrolysis assay, nucleosome remodeling assay on recombinant variant proteins Genetics in medicine High 31388190
2020 NuRD complex containing CHD4 localizes to super-enhancers where CHD4 maintains chromatin architecture permissive for PAX3-FOXO1 binding; CHD4 depletion removes HDAC2 from chromatin, increases and spreads histone acetylation, and prevents RNA Polymerase 2 positioning at promoters, impeding transcription initiation. CRISPR screen for NuRD members, ChIP-seq, ATAC-seq, gene expression analysis eLife High 32744500
2021 ZNF410 knockout reduces CHD4 levels and de-represses fetal globin genes; ZNF410 binding sites cluster exclusively near CHD4 and fully account for ZNF410's effect on HbF repression. CHD4 reduction to ~40% of normal is sufficient for substantial fetal hemoglobin de-repression. CRISPR-Cas9 screen, ChIP-seq, gene expression analysis, xenotransplantation Nature genetics High 33859416
2022 CHD4 is recruited by core cardiac transcription factors GATA4, NKX2-5, and TBX5 to specific cardiac target gene loci; CHD4 interactions with these TFs were demonstrated by mass spectrometry and Co-IP during embryonic heart development. Genetic deletion of CHD4-regulated silencer elements at Acta1 and Myh11 causes misexpression of skeletal/smooth muscle genes in the embryonic heart. Mass spectrometry (IP-MS), Co-IP, ChIP-seq, RNA-seq, CRISPR deletion of cis-regulatory elements in vivo Genes & development High 35450884
2022 KSHV lncRNA binding competes with CHD4 DNA binding; KSHV reactivation sequesters CHD4 from the viral genome (along with ADNP), and KSHV episomes localize with CHD4 and ADNP (ChAHP complex components) at genomic docking sites. ChIP, immunofluorescence, RNA-IP, viral reactivation assay Cell reports Medium 35545047
2022 RNA inhibits CHD4 (and Drosophila dMi-2) chromatin binding and nucleosome remodeling activity by competing with the nucleosome substrate; CHD4 binds G-rich RNA via two intrinsically disordered regions. This RNA-mediated inhibition is evolutionarily conserved. iCLIP, in vitro nucleosome remodeling assay, RNase treatment, pharmacological transcription inhibition, domain-deletion binding assays Cell reports High 35649367
2022 The C-terminal region of CHD4 contains an auto-inhibitory domain that contacts the helicase domain; auto-inhibition is relieved by a C-terminal SANT-SLIDE domain (split by ~150 disordered residues) likely through substrate DNA binding. An N-terminal IDR promotes remodeling integrity in a composition-dependent (not sequence-dependent) manner. In vitro ATPase and nucleosome remodeling assays with domain-deletion and chimeric constructs, single-molecule assays Nature communications High 36473839
2021 CHD4 directly binds the PLS3 promoter and activates PLS3 transcription as part of CHD4/NuRD; siRNA knockdown and overexpression experiments co-regulate CHD4 and PLS3 expression; dual-luciferase assay confirms NuRD-dependent promoter activation. ChIP, siRNA knockdown/overexpression, dual-luciferase reporter assay American journal of human genetics Medium 36812914
2021 CHD4 binds the MafA region 3 enhancer and regulates insulin secretion; Pdx1 dynamically interacts with Chd4 in islet β-cells under physiological and stimulatory conditions. Pdx1:Chd4 interactions are compromised under metabolic stress and in human T2D donor islets. Co-IP, ChIP-seq, insulin secretion assay, gene expression analysis, human islet analysis Journal of molecular endocrinology Medium 35521759
2022 CHD4 regulates chromatin accessibility to conceal aberrant CTCF-binding sites embedded in H3K9me3-enriched B2 SINE heterochromatin; CHD4 depletion causes aberrant CTCF binding within TADs and local TAD disorganization. RNA-binding IDRs of CHD4 are required to prevent aberrant CTCF binding. ChIP-seq, ATAC-seq, Hi-C, CHD4 depletion, domain-deletion constructs Molecules and cells Medium 34764232
2023 A CHD4 missense mutation (M202I in human; M195I in mouse) causes ventricular noncompaction; the mutant CHD4 protein shows augmented affinity for BRG1 (SWI/SNF), resulting in failure to derepress Adamts1 transcription. ADAMTS1 administration rescues the hypertrabeculation defect. Humanized knock-in mouse, IP-MS, ChIP, transcriptomic profiling, exogenous ADAMTS1 rescue experiment Circulation research High 37254794
2024 CHD4 interacts with SMYD1 (a striated muscle histone methyltransferase) in cardiomyocytes; CHD4 and SMYD1 repress a common set of genes involved in glycolysis, hypoxia response, and angiogenesis in developing mouse hearts. Quantitative proteomics (IP-MS), conditional KO mice (Smyd1 and Chd4), RNA-seq, ATAC-seq Development High 38619323
2024 CHD4 acts as a chromatin proofreading enzyme that promotes nucleosome positioning over GATA3 binding motifs to prevent inappropriate TF-DNA interaction; CHD4 depletion leads to redistribution of transcription factors to previously unoccupied sites and prevents inappropriate chromatin opening during GATA3-induced reprogramming. CHD4 depletion, ATAC-seq, ChIP-seq, reprogramming assays, MNase-seq for nucleosome positioning Nucleic acids research High 38281186
2024 FBXW7 degrades CHD4 protein via ubiquitin-proteasome-mediated proteolysis; CHD4 promotes nuclear translocation of β-catenin and activates the Wnt/β-catenin pathway. The FBXW7-CHD4-Wnt/β-catenin axis controls cancer stemness in TNBC. IP-MS identifying CHD4 as FBXW7 substrate, ubiquitination assay, Co-IP, protein stability assay, β-catenin localization Journal of translational medicine Medium 38268032
2024 NEAT1 lncRNA accumulates at promoter-associated DSBs following DNA damage in an m6A (METTL3)-dependent manner; m6A-modified NEAT1 releases CHD4 to allow fine-tuning of histone acetylation at DSBs. NEAT1 depletion impairs DSB focus formation. m6A mapping, NEAT1 depletion, CHD4 localization by immunofluorescence, CLIP, histone acetylation analysis Genes & development Medium 39362776
2007 In Xenopus, CHD4/Mi-2β gain- and loss-of-function experiments shifted the neuroectoderm/mesoderm boundary by regulating Sip1 and Xbra gene transcription. CHD4 suppresses Sip1 transcription by direct binding to the 5' end of the Sip1 gene body, and CHD4/Sip1 epistasis determines the threshold for Nodal-dependent Xbra induction. Xenopus gain/loss-of-function experiments, ChIP, epistasis analysis Genes & development High 17438000
2013 Chd4 and associated proteins (Hdac1/2, Kap1, Cbx1) bind at -207/-148 of the Sox9 promoter (shown by ChIP) and act as corepressors of Sox9 expression during BMP-2-induced chondrogenesis; let-7a miRNA targets the 3'UTR of Chd4 to promote chondrogenesis. ChIP, nuclease hypersensitivity assay, quantitative proteomics (iTRAQ), let-7a functional assay Journal of bone and mineral research Medium 23519980
2022 In the heart, CHD4 physically interacts with the transcription factor Znf219; Znf219 represses skeletal-muscle sarcomere programs in cardiomyocytes in a manner similar to Chd4, and knockdown of Znf219 causes arrhythmias in mice. Co-IP, cardiac-specific Znf219 knockdown mouse, ECG analysis, gene expression International journal of molecular sciences Medium 36076959
2013 CHD4/NuRD maintains unmethylated rDNA promoters by directly binding and repressing the TIP5 promoter (a component of the NoRC complex that recruits DNA methyltransferases to rDNA). Deficiency of NuRD activates TIP5, increasing rDNA methylation and transcriptional silencing. ChIP at TIP5 promoter, NuRD component knockdown, bisulfite sequencing, rRNA transcription assay Biochemical and biophysical research communications Medium 23796711

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. The EMBO journal 299 20693977
2010 The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage. The Journal of cell biology 188 20805324
2017 CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes. Cancer cell 153 28486105
2018 Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes. Nature 151 29795351
2015 Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4. Genes & development 138 25737278
2011 Plant homeodomain (PHD) fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9. The Journal of biological chemistry 133 21278251
2016 De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms. American journal of human genetics 111 27616479
2014 ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state. Cell reports 99 24440720
2018 lncRNA PAPAS tethered to the rDNA enhancer recruits hypophosphorylated CHD4/NuRD to repress rRNA synthesis at elevated temperatures. Genes & development 96 29907651
2006 NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex. The Journal of biological chemistry 96 16574654
2012 Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression. Proceedings of the National Academy of Sciences of the United States of America 93 22215588
2009 Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. The Biochemical journal 93 19624289
2017 CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality. Nucleic acids research 90 28977666
2012 Chromodomain helicase DNA-binding protein 4 (CHD4) regulates homologous recombination DNA repair, and its deficiency sensitizes cells to poly(ADP-ribose) polymerase (PARP) inhibitor treatment. The Journal of biological chemistry 85 22219182
2010 The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea. Development (Cambridge, England) 85 20223763
2013 CHD4 in the DNA-damage response and cell cycle progression: not so NuRDy now. Biochemical Society transactions 81 23697937
2015 Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma. Journal of hepatology 78 26095183
1999 Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4. Biochemistry 78 10545197
2020 ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. Molecular cell 73 33301730
2013 The chromodomain helicase Chd4 is required for Polycomb-mediated inhibition of astroglial differentiation. The EMBO journal 72 23624931
2013 Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity. Proceedings of the National Academy of Sciences of the United States of America 71 23471993
2020 SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair. Nucleic acids research 70 31970415
2020 Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations. eLife 67 32543371
2019 The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis. Genetics in medicine : official journal of the American College of Medical Genetics 66 31388190
2012 The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4. Journal of molecular biology 64 22575888
2018 Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency. Cell stem cell 62 30122475
2016 CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex. The Journal of biological chemistry 62 27235397
2021 ZNF410 represses fetal globin by singular control of CHD4. Nature genetics 59 33859416
2018 CHD3 and CHD4 recruitment and chromatin remodeling activity at DNA breaks is promoted by early poly(ADP-ribose)-dependent chromatin relaxation. Nucleic acids research 57 29733391
2016 The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis. Cell metabolism 55 27166947
2020 Chd4 choreographs self-antigen expression for central immune tolerance. Nature immunology 53 32601470
2015 Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation. Blood 53 26265695
2019 The pleiotropy associated with de novo variants in CHD4, CNOT3, and SETD5 extends to moyamoya angiopathy. Genetics in medicine : official journal of the American College of Medical Genetics 51 31474762
2020 CHD4 Promotes Breast Cancer Progression as a Coactivator of Hypoxia-Inducible Factors. Cancer research 50 32699137
2016 Helicase CHD4 is an epigenetic coregulator of PAX3-FOXO1 in alveolar rhabdomyosarcoma. The Journal of clinical investigation 48 27760049
2015 The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose). The Journal of biological chemistry 48 26565020
2020 The chromatin remodeling enzyme Chd4 regulates genome architecture in the mouse brain. Nature communications 47 32647123
2020 NuRD subunit CHD4 regulates super-enhancer accessibility in rhabdomyosarcoma and represents a general tumor dependency. eLife 45 32744500
2017 The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes. The Journal of biological chemistry 44 28298436
2017 EZH2-, CHD4-, and IDH-linked epigenetic perturbation and its association with survival in glioma patients. Journal of molecular cell biology 44 29272522
2018 CHD4 and the NuRD complex directly control cardiac sarcomere formation. Proceedings of the National Academy of Sciences of the United States of America 42 29891665
2012 MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes. Molecular and cellular biology 41 23071088
2022 KSHV episome tethering sites on host chromosomes and regulation of latency-lytic switch by CHD4. Cell reports 38 35545047
2020 Knockdown of circ_0006528 Suppresses Cell Proliferation, Migration, Invasion, and Adriamycin Chemoresistance via Regulating the miR-1236-3p/CHD4 Axis in Breast Cancer. The Journal of surgical research 36 33333383
2019 CHD4 is essential for transcriptional repression and lineage progression in B lymphopoiesis. Proceedings of the National Academy of Sciences of the United States of America 36 31085655
2015 Acetyltransferase p300 collaborates with chromodomain helicase DNA-binding protein 4 (CHD4) to facilitate DNA double-strand break repair. Mutagenesis 36 26546801
2013 The NuRD chromatin-remodeling enzyme CHD4 promotes embryonic vascular integrity by transcriptionally regulating extracellular matrix proteolysis. PLoS genetics 36 24348274
2016 RNAi screens identify CHD4 as an essential gene in breast cancer growth. Oncotarget 35 27779108
2012 The chromatin-remodeling enzymes BRG1 and CHD4 antagonistically regulate vascular Wnt signaling. Molecular and cellular biology 35 22290435
2020 CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A. BMC cancer 34 32228507
2022 CHD4 is recruited by GATA4 and NKX2-5 to repress noncardiac gene programs in the developing heart. Genes & development 33 35450884
2011 ATM mediated phosphorylation of CHD4 contributes to genome maintenance. Genome integrity 33 21219611
2023 Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies. Annals of the rheumatic diseases 32 37130727
2019 CHD4 regulates the DNA damage response and RAD51 expression in glioblastoma. Scientific reports 31 30872624
2018 CHD4-mediated loss of E-cadherin determines metastatic ability in triple-negative breast cancer cells. Experimental cell research 31 29305962
2022 CHD4 promotes acquired chemoresistance and tumor progression by activating the MEK/ERK axis. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 30 36603431
2012 Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4. FEBS letters 29 22749909
2018 CHD4 mutations promote endometrial cancer stemness by activating TGF-beta signaling. American journal of cancer research 28 29888111
2020 CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation. Nature communications 27 32251276
2016 CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity. The Journal of clinical investigation 27 27140400
2018 The chromatin-remodeling factor CHD4 is required for maintenance of childhood acute myeloid leukemia. Haematologica 26 29599201
2013 CHD4 is a RanGTP-dependent MAP that stabilizes microtubules and regulates bipolar spindle formation. Current biology : CB 24 24268414
2019 The chromodomain helicase CHD4 regulates ERBB2 signaling pathway and autophagy in ERBB2+ breast cancer cells. Biology open 22 30967373
2022 Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development. Epigenetics & chromatin 19 35568926
2021 CHD4 regulates platinum sensitivity through MDR1 expression in ovarian cancer: A potential role of CHD4 inhibition as a combination therapy with platinum agents. PloS one 19 34161330
2021 CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia. CNS neuroscience & therapeutics 18 34109749
2021 CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration. Stem cell reports 18 34450038
2019 The NuRD chromatin-remodeling complex enzyme CHD4 prevents hypoxia-induced endothelial Ripk3 transcription and murine embryonic vascular rupture. Cell death and differentiation 18 31235857
2021 A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool. Stem cell reports 16 33961790
2021 CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer. International journal of biological sciences 16 33994851
2019 Distinct Requirements of CHD4 during B Cell Development and Antibody Response. Cell reports 16 31042474
2016 Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis. Scientific reports 16 27805061
2023 Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1. Circulation research 15 37254794
2021 CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells. International journal of molecular sciences 15 33419089
2013 Chd4 and associated proteins function as corepressors of Sox9 expression during BMP-2-induced chondrogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 15 23519980
2021 Role of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Cancer. Frontiers in oncology 14 33981601
2014 Association of the chromodomain helicase DNA-binding protein 4 (CHD4) missense variation p.D140E with cancer: potential interaction with smoking. Genes, chromosomes & cancer 14 25407497
2024 Fbxw7 suppresses carcinogenesis and stemness in triple-negative breast cancer through CHD4 degradation and Wnt/β-catenin pathway inhibition. Journal of translational medicine 13 38268032
2023 The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer. Journal of translational medicine 13 36681835
2022 ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers. BMC biology 13 36153585
2018 The nucleosome remodeling and deacetylase complex protein CHD4 regulates neural differentiation of mouse embryonic stem cells by down-regulating p53. The Journal of biological chemistry 13 30409903
2024 CHD4 R975H mutant activates tumorigenic pathways and promotes stemness and M2-like macrophage polarization in endometrial cancer. Scientific reports 12 39127769
2013 CHD4/NuRD maintains demethylation state of rDNA promoters through inhibiting the expression of the rDNA methyltransferase recruiter TIP5. Biochemical and biophysical research communications 12 23796711
2024 CHD4 and SMYD1 repress common transcriptional programs in the developing heart. Development (Cambridge, England) 11 38619323
2024 NEAT1 promotes genome stability via m6A methylation-dependent regulation of CHD4. Genes & development 11 39362776
2023 Epigenetic regulation of plastin 3 expression by the macrosatellite DXZ4 and the transcriptional regulator CHD4. American journal of human genetics 11 36812914
2022 Unclassified Neuroendocrine Tumor with a Novel CHD4::AFF2 Fusion: Expanding the Family of AFF2-Rearranged Head and Neck Malignancies. Head and neck pathology 11 35218513
2007 CHD4/Mi-2beta activity is required for the positioning of the mesoderm/neuroectoderm boundary in Xenopus. Genes & development 11 17438000
2024 The Chromatin Remodeler CHD4 Sustains Ewing Sarcoma Cell Survival by Controlling Global Chromatin Architecture. Cancer research 10 37963210
2022 CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice†. Biology of reproduction 10 35980806
2021 CHD4 Conceals Aberrant CTCF-Binding Sites at TAD Interiors by Regulating Chromatin Accessibility in Mouse Embryonic Stem Cells. Molecules and cells 10 34764232
2021 Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination. Immunological reviews 10 34927255
2022 Divergent regulatory roles of NuRD chromatin remodeling complex subunits GATAD2 and CHD4 in Caenorhabditis elegans. Genetics 9 35323946
2022 The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function. Journal of molecular endocrinology 9 35521759
2022 RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodeling. Cell reports 9 35649367
2022 The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families. Nature communications 9 36473839
2024 Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4. Nucleic acids research 8 38281186
2022 Interplay between the Chd4/NuRD Complex and the Transcription Factor Znf219 Controls Cardiac Cell Identity. International journal of molecular sciences 8 36076959
2019 The Tale of CHD4 in DNA Damage Response and Chemotherapeutic Response. Journal of cancer research and cellular therapeutics 8 32577620
2022 CHD4 orchestrates the symphony of T and B lymphocytes development and a good mediator in preventing from autoimmune disease. Immunity, inflammation and disease 7 35759243