Affinage

CHD4

ATP-dependent chromatin remodeler CHD4 · UniProt Q14839

Length
1912 aa
Mass
218.0 kDa
Annotated
2026-06-09
100 papers in source corpus 61 papers cited in narrative 61 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

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 nucleosome remodeling and deacetylase complex, where it is a peripheral subunit whose addition to a stable HDAC-containing core reconstitutes nucleosome remodeling activity (PMID:27235397). Mechanistically, CHD4 slides nucleosomes by distorting DNA at the SHL +2 position without unwrapping terminal DNA, a feature consistent with its repressive role (PMID:32543371), and it decouples continuous entry-side DNA translocation from concerted 4–6 bp exit-side steps via a strain-buildup (twist-defect) mechanism (PMID:32251276). Its activity is governed by intramolecular allostery among its tandem PHD fingers, chromodomains, helicase, and C-terminal regions (PMID:22575888, PMID:36473839): the PHD fingers bivalently engage two histone H3 N-terminal tails with preference for unmodified H3K4 and methylated/acetylated H3K9, an interaction required for repression and for displacing HP1γ from H3K9me3-marked chromatin (PMID:19624289, PMID:22215588), while an N-terminal IDR supports remodeling integrity and a C-terminal auto-inhibitory region is relieved by SANT-SLIDE DNA binding (PMID:36473839). CHD4 is targeted to specific loci by transcription factors—including cardiac GATA4/NKX2-5/TBX5 to repress noncardiac myofibril programs (PMID:35450884, PMID:29891665), GATA3 in T cells (PMID:23471993), and ADNP/HP1 in the ChAHP complex (PMID:29795351)—and by lncRNAs such as PAPAS via DNA-RNA triplex tethering (PMID:29907651). In the DNA damage response, CHD4 is recruited to double-strand breaks in a poly(ADP-ribosyl)ation-dependent manner (PMID:20693977, PMID:29733391), is phosphorylated by ATM (PMID:21219611), and promotes RNF168/BRCA1 chromatin assembly, chromatin relaxation, and homologous recombination (PMID:20805324, PMID:31970415). CHD4 also functions independently of chromatin as a RanGTP-dependent microtubule-associated protein that stabilizes the mitotic spindle (PMID:24268414). Globally, it represses lineage-inappropriate gene programs, restricts chromatin accessibility, and controls genome architecture by limiting aberrant cohesin and CTCF occupancy (PMID:32647123, PMID:34764232), and RNA binding to its intrinsically disordered regions provides a transcription-coupled brake on its remodeling activity (PMID:35649367). A de novo CHD4 missense mutation that augments its affinity for endocardial BRG1 causes biventricular hypertrabeculation through ADAMTS1 misregulation (PMID:37254794).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 Medium

    Established that CHD4 physically links a chromatin deacetylase/remodeling complex to DNA-damage checkpoint signaling, anchoring it within the NuRD complex.

    Evidence Biochemical co-purification, mass spectrometry, and Co-IP showing CHD4 associates with ATR, HDAC1/2, and MTA proteins

    PMID:10545197

    Open questions at the time
    • Did not establish whether the ATR association is direct or NuRD-mediated
    • No functional consequence of the CHD4-ATR link demonstrated
  2. 2009 High

    Defined the histone-mark code read by CHD4's PHD2 finger, explaining how CHD4 is recruited to and discriminates among modified nucleosomes.

    Evidence Fluorescence/NMR binding assays, peptide library screen, and mutagenesis quantifying PHD2-H3 tail affinities

    PMID:19624289

    Open questions at the time
    • Binding measured on peptides, not nucleosomes
    • Did not address how mark reading is coupled to ATPase activity
  3. 2010 High

    Demonstrated CHD4's direct role in the DNA damage response, showing PAR-dependent recruitment, ATM phosphorylation, and control of RNF168/BRCA1 assembly and the G1/S transition.

    Evidence Two independent studies using laser micro-irradiation, kinase assays, MS screens, immunofluorescence, FRAP, and clonogenic survival

    PMID:20693977 PMID:20805324

    Open questions at the time
    • Did not resolve whether PAR recruitment is direct binding or indirect
    • Mechanism linking remodeling activity to RNF168/BRCA1 loading not defined
  4. 2012 High

    Showed that CHD4's PHD, chromo, and helicase domains communicate allosterically to regulate ATPase and remodeling activity, and that multivalent dual-H3-tail engagement underlies NuRD repression and HP1γ displacement.

    Evidence SAXS, cross-linking MS, limited proteolysis, ATPase/remodeling assays, NMR, and chromatin immunofluorescence across multiple studies

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

    Open questions at the time
    • No atomic-resolution structure of the full multidomain protein on a nucleosome
    • How transcription-factor recruitment intersects with allosteric regulation unresolved
  5. 2013 High

    Revealed a chromatin-independent function: CHD4 acts as a RanGTP-dependent microtubule-associated protein required for bipolar spindle assembly.

    Evidence Xenopus egg extract immunodepletion, RNAi in HeLa and S2 cells, MT-binding and spindle assembly assays

    PMID:24268414

    Open questions at the time
    • Structural basis of MT binding not defined
    • Relationship between spindle role and NuRD function unclear
  6. 2016 High

    Positioned CHD4 as a peripheral, exchangeable catalytic subunit of NuRD whose recruitment confers remodeling onto a stable deacetylase core.

    Evidence Biochemical reconstitution with HDAC and nucleosome remodeling activity assays

    PMID:27235397

    Open questions at the time
    • Stoichiometry and dynamics of CHD4 exchange in vivo not addressed
    • Whether peripheral architecture differs across NuRD subtypes unknown
  7. 2018 High

    Identified CHD4 as the master genomic effector through which transcription factors and lncRNAs enforce lineage-specific repression, including ZNF410-driven CHD4 expression controlling fetal globin and ADNP-directed ChAHP repression.

    Evidence CRISPR screens, ChIP-seq, ATAC-seq, crystallography of ZNF410-DNA, RNA-triplex and protein-RNA interaction assays, conditional knockouts across multiple tissues

    PMID:27166947 PMID:29795351 PMID:29891665 PMID:29907651 PMID:33301730

    Open questions at the time
    • How distinct recruiters compete for a limited CHD4 pool not resolved
    • Whether repression at all loci requires catalytic remodeling or only occupancy unclear
  8. 2020 High

    Provided the mechanistic basis of CHD4 remodeling, showing it distorts DNA at SHL +2 without unwrapping terminal DNA and decouples entry- and exit-side translocation through strain buildup.

    Evidence Cryo-EM at 3.1 Å with AMP-PNP and single-molecule fluorescence/optical tweezer assays with ATPase-dead mutants

    PMID:32251276 PMID:32543371

    Open questions at the time
    • Structures lack the regulatory N- and C-terminal domains in context
    • How allosteric inputs modulate the twist-defect step not visualized
  9. 2022 High

    Defined autoregulatory and RNA-mediated brakes on CHD4: a C-terminal auto-inhibitory region relieved by SANT-SLIDE DNA binding, and a conserved RNA-IDR interaction that competes with nucleosome substrate to inhibit remodeling.

    Evidence Single-molecule and ATPase/remodeling assays with domain constructs, SAXS, and iCLIP with in vitro RNA competition assays

    PMID:35649367 PMID:36473839

    Open questions at the time
    • In vivo significance of RNA inhibition during transcription not quantified
    • How IDR composition tunes activity at specific loci unclear
  10. 2023 High

    Linked a de novo CHD4 missense mutation to a developmental phenotype, showing gain of BRG1 affinity disrupts cardiac trabeculation termination via ADAMTS1.

    Evidence Humanized mouse model with Co-IP-MS, ChIP, transcriptomics, and ADAMTS1 genetic rescue

    PMID:37254794

    Open questions at the time
    • Whether the gain-of-function mechanism generalizes to other CHD4 patient mutations unknown
    • Structural basis of enhanced BRG1 binding not defined
  11. 2024 Medium

    Extended CHD4's role to genome surveillance and proof-reading, positioning nucleosomes over transcription-factor motifs and being released from damage-associated lncRNAs to fine-tune chromatin.

    Evidence ATAC-seq, ChIP-seq, reprogramming assays, and m6A-seq with NEAT1 depletion

    PMID:38281186 PMID:39362776

    Open questions at the time
    • Direct biochemical demonstration of competitive nucleosome positioning at TF motifs lacking
    • Generality of lncRNA-mediated CHD4 release across damage contexts unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many competing recruiters (sequence-specific TFs, lncRNAs, DDR signals, and inhibitory RNAs) are integrated to direct a limited cellular CHD4 pool to the correct loci at the correct time remains unresolved.
  • No quantitative model partitioning CHD4 among NuRD, ChAHP, and NuRD-independent pools
  • Structural picture of full-length CHD4 with regulatory domains engaged on a nucleosome lacking
  • Rules governing activation versus repression at TF-recruited loci undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0003723 RNA binding 3 GO:0042393 histone binding 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3 GO:0140657 ATP-dependent activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2
Partners
ADNPBRG1GATA3GATA4HDAC2HP1MTA1ZNF410
Complex memberships
ChAHPNuRD

Evidence

Reading pass · 61 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 CHD4 is recruited to DNA-damage sites in a poly(ADP-ribose)-dependent manner and is phosphorylated by ATM kinase. CHD4 promotes repair of DNA double-strand breaks and controls the G1/S cell-cycle transition by regulating p53 deacetylation. Co-immunoprecipitation, kinase assay, laser micro-irradiation, cell-cycle analysis, loss-of-function (siRNA/shRNA knockdown) The EMBO journal High 20693977
2010 CHD4 knockdown disrupts the chromatin response at the level of RNF168 ubiquitin ligase, impairing local ubiquitylation and BRCA1 assembly at DNA double-strand breaks, and causes enhanced Cdc25A degradation and p21(Cip1) accumulation leading to extended cell cycle delay. Mass spectrometry screen, siRNA knockdown, immunofluorescence, FRAP, clonogenic survival assays The Journal of cell biology High 20805324
1999 CHD4 (Mi-2beta) physically associates with ATR kinase and with HDAC2, and other NuRD complex members (HDAC1, MTA1, MTA2) are also detectable in ATR immunoprecipitates, linking the DDR checkpoint kinase to the NuRD chromatin remodeling/deacetylation complex. Biochemical co-purification, tandem mass spectrometric sequencing, co-immunoprecipitation Biochemistry Medium 10545197
2009 The second PHD finger (PHD2) of CHD4 binds the N-terminus of histone H3; binding is enhanced by H3K9 acetylation (Kd ~0.6 µM) or methylation (H3K9me3, Kd ~0.9 µM) and inhibited by H3K4 methylation (Kd drops to ~2.0 mM) or H3A1 acetylation; phosphorylation of H3T3, T6, or S10 abolishes binding. Tryptophan fluorescence binding assay, NMR, peptide library screen, mutagenesis, data-driven docking The Biochemical journal High 19624289
2011 Solution structure of CHD4 PHD2 in complex with H3K9me3 was determined by NMR, revealing a cation-π recognition mechanism for methylated Lys9. Both PHD1 and PHD2 can bind H3 N-terminal tails, suggesting CHD4 can engage two H3 tails simultaneously on one or two nucleosomes. NMR structure determination, fluorescence binding assays, mutagenesis The Journal of biological chemistry High 21278251
2012 Tandem PHD1/2 fingers of CHD4 engage nucleosomes multivalently by simultaneously binding two histone H3 tails; this robust synergistic interaction displaces HP1γ from pericentric sites, disperses the H3K9me3 mark, and is required for the repressive activity of CHD4/NuRD complex. NMR, fluorescence binding assays, chromatin immunofluorescence, mutagenesis, functional repression assay Proceedings of the National Academy of Sciences of the United States of America High 22215588
2012 CHD4 chromodomains, ATPase/helicase, and C-terminal domains are all required for transcriptional repression by NuRD. The chromodomains, ATPase, and PHD domains (but not the CTD) are required for efficient CHD4 association with promoter chromatin. Loss of MBD2 or DNA methylation impairs CHD4 chromatin association. Domain deletion/mutation analysis, chromatin immunoprecipitation (ChIP), reporter gene assays, loss-of-function studies Molecular and cellular biology Medium 23071088
2012 The PHD and chromo domains regulate CHD4 ATPase activity through intramolecular allosteric communication; SAXS-based shape reconstruction reveals extensive domain-domain interactions that govern the overall regulation of chromatin remodeling. Small-angle X-ray scattering (SAXS), nucleosome binding ATPase assay, remodeling assay, limited proteolysis, cross-linking and tandem mass spectrometry Journal of molecular biology High 22575888
2012 CHD4 PHD, chromo, and helicase domains regulate ATPase activity through intramolecular allostery; DNA binding, histone binding, and ATPase activities are functionally interdependent. Domain deletion constructs, ATPase assay, DNA/histone binding assay, SAXS molecular shape reconstruction FEBS letters Medium 22749909
2011 ATM kinase phosphorylates CHD4 in response to ionizing radiation, and this phosphorylation promotes increased chromatin binding/retention and assembly of CHD4 foci at DNA damage sites; phospho-mutant CHD4 (non-phosphorylatable by ATM) fails to show enhanced chromatin retention and causes high rates of spontaneous DNA damage. Immunofluorescence, chromatin fractionation, phosphorylation assay, overexpression of phospho-mutant, cell survival analysis Genome integrity Medium 21219611
2012 CHD4 is a BRIT1 (MCPH1) binding partner required for BRIT1 recruitment to DNA damage lesions; BRIT1's BRCT domains mediate interaction with CHD4. CHD4 ATPase-dead mutant impairs BRIT1 recruitment. CHD4 deficiency impairs BRCA1 recruitment and HR repair efficiency, and sensitizes cells to PARP inhibitors. Co-immunoprecipitation, domain mapping, laser micro-irradiation, siRNA knockdown, HR reporter assay, PARP inhibitor sensitivity assay The Journal of biological chemistry Medium 22219182
2006 NAB2 transcriptional repression requires interaction with the CHD4 subunit of NuRD through a specific NAB2 repression domain; both NAB proteins can bind CHD3 or CHD4; CHD4 is required for NAB2-mediated repression of the endogenous Rad gene and co-localizes with NAB2 on the Rad promoter in myelinating Schwann cells; the NAB2-CHD4 interaction is regulated by alternative splicing. Co-immunoprecipitation, domain deletion analysis, ChIP, reporter gene assay The Journal of biological chemistry Medium 16574654
2015 The N-terminal region of CHD4 contains a stable HMG box-like domain (CHD4-N) that binds poly(ADP-ribose) with higher affinity than DNA; the full N-terminal region (but not CHD4-N alone) is essential for full nucleosome remodeling activity and for localizing CHD4 to DNA damage sites. X-ray crystallography (structure determination), poly(ADP-ribose) binding assays, DNA binding assays, remodeling assay, laser micro-irradiation localization The Journal of biological chemistry High 26565020
2016 CHD4 is a peripheral (not central hub) component of the NuRD complex; a NuRD sub-complex lacking CHD4 retains HDAC activity as a stable species; addition of recombinant CHD4 to this nucleosome deacetylase complex reconstitutes NuRD with nucleosome remodeling activity. Biochemical reconstitution, HDAC activity assay, nucleosome remodeling assay, Co-immunoprecipitation The Journal of biological chemistry High 27235397
2018 PAPAS lncRNA tethers to rDNA enhancer via DNA-RNA triplex and recruits CHD4/NuRD through direct interaction between the N-terminal part of CHD4 and an unstructured A-rich region in PAPAS; heat stress-dependent dephosphorylation of CHD4 at three serine residues enhances CHD4/NuRD-RNA interaction and reinforces rDNA transcription repression. RNA-protein interaction assays, RNA secondary structure mapping, DNA-RNA triplex assay, phosphorylation analysis, deletion/mutation analysis, ChIP Genes & development High 29907651
2017 CHD3 and CHD4 form distinct, isoform-specific NuRD complexes (monomeric ATPase each); both exhibit similar intranuclear mobility and accumulate at UV-induced DNA repair sites; CHD3 and CHD4 differ in nuclear localization patterns, target genes, and nucleosome remodeling/positioning behavior in vitro. Co-immunoprecipitation, FRAP (fluorescence recovery after photobleaching), in vitro nucleosome remodeling assay, transcriptomic analysis, live-cell imaging Nucleic acids research High 28977666
2018 CHD4 interacts with ADNP and HP1 to form the stable ChAHP complex; ADNP mediates complex assembly and recognizes DNA motifs specifying ChAHP binding to euchromatin; ChAHP represses lineage-specific genes by establishing inaccessible chromatin in a locally restricted, H3K9me3-independent manner. Co-immunoprecipitation, mass spectrometry, ATAC-seq, ChIP-seq, genetic ablation in mouse ES cells Nature High 29795351
2013 CHD4 is a RanGTP-dependent microtubule-associated protein (MAP) that stabilizes microtubules during mitosis independently of its chromatin remodeling activity; CHD4 binds MTs via its NLS-containing chromatin-binding region, partially localizes to the spindle in mitosis, and its depletion prevents spindle assembly and causes chromosome missegregation. Xenopus egg extract immunodepletion, RNAi in HeLa and Drosophila S2 cells, live-cell imaging, MT binding assay, spindle assembly assay Current biology : CB High 24268414
2013 CHD4 (Chd4) physically interacts with the PcG protein Ezh2 and is required specifically for PcG-mediated suppression of the GFAP astrogenic marker gene; in vivo depletion of Chd4 in the developing neocortex promotes astrogenesis. Co-immunoprecipitation, in vivo Chd4 knockdown, immunofluorescence, gene expression analysis The EMBO journal Medium 23624931
2013 GATA3 forms functionally distinct complexes with CHD4: a GATA3/CHD4/p300 transcriptional activation complex at Th2 cytokine loci and a GATA3/CHD4-NuRD repression complex at the Tbx21 locus in Th2 cells; CHD4 is required for Th2-dependent inflammation in vivo. Co-immunoprecipitation, ChIP, siRNA knockdown, reporter assay, in vivo asthma model Proceedings of the National Academy of Sciences of the United States of America Medium 23471993
2013 CHD4-containing NuRD complexes directly bind the promoters of uPAR and thrombospondin-1 in endothelial cells to repress uPAR and activate Thbs1, preventing excessive ECM proteolysis; loss of endothelial CHD4 leads to elevated plasmin activity and vascular rupture at midgestation. ChIP, conditional knockout mouse model, in vivo and ex vivo vascular analysis, qPCR arrays, genetic rescue (uPA reduction) PLoS genetics High 24348274
2014 ZFHX4 interacts with CHD4, a core member of the NuRD complex, in glioblastoma tumor-initiating cells; ZFHX4 and CHD4 bind overlapping genomic loci and control similar gene expression programs; ZFHX4 functions as a master regulator of CHD4 activity. Co-immunoprecipitation, ChIP-seq, gene expression analysis, siRNA knockdown, intracranial xenograft Cell reports Medium 24440720
2015 p300 physically interacts with CHD4 at DNA damage sites (dependent on CHD4's chromodomain and ATPase/helicase domain, and p300's CH2, Bd, and HAT domains); they are co-recruited to DSBs and cooperatively promote homologous recombination repair by facilitating RPA recruitment. Immunoprecipitation, purified protein pulldown, immunofluorescence, DR-GFP/EJ5-GFP reporter systems, siRNA knockdown Mutagenesis Medium 26546801
2016 CHD4 interacts with PAX3-FOXO1 oncogenic fusion protein via short DNA fragments and co-occupies regulatory regions of PAX3-FOXO1 target genes; CHD4 is an essential coregulator of PAX3-FOXO1 activity required for a subset of target gene expression and for alveolar rhabdomyosarcoma cell viability. Interactome screen, Co-immunoprecipitation, ChIP-seq, siRNA knockdown, gene expression analysis, in vivo xenograft The Journal of clinical investigation Medium 27760049
2017 CHD4 recruits repressive chromatin proteins including DNA methyltransferases to sites of oxidative DNA damage (8-OHdG), promoting de novo DNA methylation and epigenetic silencing of tumor suppressor genes; CHD4 is recruited by OGG1 for oxidative damage and by ZMYND8 for double-strand breaks. Co-immunoprecipitation, ChIP, DNA methylation assays, siRNA knockdown, cell invasion/metastasis assays Cancer cell Medium 28486105
2018 Loss of CHD4 in the heart triggers aberrant expression of the skeletal muscle gene program; loss of CHD4 in skeletal muscle causes inappropriate cardiac gene expression; in both tissues, mitochondrial function depends on CHD4/NuRD, demonstrating CHD4 maintains striated muscle identity. Tissue-specific conditional knockout mouse models, transcriptomic analysis, metabolic profiling, histology Cell metabolism High 27166947
2018 CHD4/NuRD directly represses skeletal and smooth muscle myofibril isoforms in the developing heart; CHD4 binds unique sites in smooth muscle myosin heavy chain, fast skeletal α-actin, and fast skeletal troponin complex genes; loss of CHD4 creates hybrid cardiomyocytes with intercalated skeletal and smooth muscle myofibril components disrupting sarcomere formation. Conditional knockout mouse model, transcriptomics, ChIP-seq, histology, cardiac function analysis in utero Proceedings of the National Academy of Sciences of the United States of America High 29891665
2018 CHD4 is recruited to DNA breaks by poly(ADP-ribosyl)ation (PAR)-dependent mechanism, but not through direct PAR binding; CHD4 plays an active role in chromatin remodeling at DNA breaks as part of a two-step mechanism where initial PAR-dependent relaxation (by PARP1/ALC1) promotes CHD4 recruitment for further remodeling. Live-cell fluorescence three-hybrid assay, laser micro-irradiation, siRNA knockdown, chromatin relaxation assays Nucleic acids research Medium 29733391
2019 CHD4 depletion specifically reduces CHD4 levels (~60%) and derepresses fetal hemoglobin genes in erythroid cells; ZNF410 directly and uniquely activates CHD4 transcription through two evolutionarily conserved clusters of binding sites near the CHD4 gene, and this is the primary mechanism by which ZNF410 controls fetal globin repression. CRISPR-Cas9 genetic screen, in vitro DNA binding assays, crystallography (ZNF410-DNA structure), xenotransplantation, ChIP-seq Molecular cell High 33301730
2020 Cryo-EM structure of CHD4 engaged with a nucleosome at 3.1 Å resolution shows the ATPase motor binds and distorts nucleosomal DNA at SHL +2, supporting the 'twist defect' model; CHD4 does not unwrap terminal DNA (unlike Chd1), consistent with its repressive function. Cryo-electron microscopy (cryo-EM) structure determination at 3.1 Å with AMP-PNP eLife High 32543371
2020 Single-molecule assays reveal that CHD4 binding energy alone (without ATP) triggers conformational changes in nucleosomal DNA at the entry side; during remodeling, entry-side DNA enters continuously while exit-side DNA moves in concerted 4–6 bp steps, indicating CHD4 decouples entry- and exit-side DNA translocation through a strain-buildup mechanism. Single-molecule fluorescence assays, optical tweezers, ATPase-dead mutant analysis Nature communications High 32251276
2020 SIRT6 interacts with CHD4 upon DNA damage and recruits CHD4 to damage sites in an ATM-dependent process; CHD4 displaces HP1 from H3K9me3 at damage sites to promote chromatin relaxation; this SIRT6-CHD4 axis is specifically required for HR in compacted chromatin during G2 phase. Co-immunoprecipitation, laser micro-irradiation, siRNA knockdown, chromatin accessibility assay, HR reporter assay Nucleic acids research Medium 31970415
2020 CHD4 physically interacts with HIF1α and HIF2α subunits and enhances HIF-driven transcription; under normoxia CHD4 enrichment at HIF target gene promoters increases RNA Pol II loading through p300; hypoxia promotes CHD4 chromatin binding via HIF1/2α and CHD4 in turn enhances HIF1α recruitment. Co-immunoprecipitation, ChIP, loss-of-function (siRNA/shRNA), in vivo xenograft Cancer research Medium 32699137
2020 Conditional knockout of Chd4 in cerebellar granule neurons increases genome-wide chromatin accessibility and promotes cohesin recruitment preferentially to gene enhancers; loss of Chd4 strengthens interactions among developmentally repressed contact domains and genomic loops, correlating with increased enhancer activity and cohesin occupancy. Conditional knockout mouse model, ATAC-seq, Hi-C, ChIP-seq, in vivo profiling Nature communications High 32647123
2020 Chd4 plays a key role in self-antigen expression in medullary thymic epithelial cells (mTECs) by organizing promoter regions of Fezf2-dependent genes and contributing to Aire-mediated self-antigen induction via super-enhancers; Chd4-deficient mTECs show impaired T cell tolerance and autoimmune phenotypes. Conditional knockout mouse model, gene expression analysis, ChIP-seq, immunophenotyping Nature immunology High 32601470
2019 CHD4 regulates RAD51 expression transcriptionally in glioblastoma cells, providing a mechanism by which CHD4 promotes DNA damage resistance; CHD4 suppression defects both the DNA damage response and RAD51 expression. siRNA/shRNA knockdown, western blot, immunofluorescence, gene expression analysis Scientific reports Medium 30872624
2022 CHD4 is recruited to NuRD super-enhancers in rhabdomyosarcoma where it generates chromatin architecture permissive for PAX3-FOXO1 binding; CHD4 depletion removes HDAC2 from chromatin, leading to spread of histone acetylation, and prevents RNA Pol II positioning at promoters, impeding transcription initiation. CRISPR NuRD screen, ChIP-seq, ATAC-seq, siRNA knockdown, gene expression analysis eLife High 32744500
2022 CHD4 is recruited by cardiac transcription factors GATA4, NKX2-5, and TBX5 to specific cardiac loci; CHD4 physically interacts with these factors and co-occupies their target gene regulatory regions to repress noncardiac gene programs; deletion of CHD4-bound silencer elements at Acta1 and Myh11 leads to inappropriate skeletal/smooth muscle gene misexpression in the heart. Mass spectrometry (Co-IP-MS), ChIP-seq, transcriptomics, conditional KO, in vivo silencer deletion Genes & development High 35450884
2022 CHD4 N-terminal intrinsically disordered region (IDR) promotes remodeling integrity in a composition- but not sequence-dependent manner; the C-terminal region harbors an auto-inhibitory region that contacts the helicase domain; auto-inhibition is relieved by a C-terminal SANT-SLIDE domain that binds substrate DNA. Single-molecule assays, domain deletion/swap constructs, ATPase assay, nucleosome remodeling assay, SAXS Nature communications High 36473839
2022 RNA inhibits CHD4 chromatin binding and nucleosome remodeling activity; CHD4 binds G-rich RNA via two intrinsically disordered regions; RNA competes with nucleosome substrate to inhibit CHD4-mediated nucleosome mobilization; this mechanism is evolutionarily conserved between Drosophila dMi-2 and human CHD4. iCLIP (individual nucleotide resolution CLIP), in vitro RNA binding assay, nucleosome remodeling assay, pharmacological transcription inhibition, RNase digestion Cell reports High 35649367
2021 ZNF410 knockout reduces CHD4 levels by ~60% and substantially de-represses fetal hemoglobin genes; ZNF410 regulates fetal globin exclusively through CHD4, and two CHD4 genomic regulatory clusters with 27 combined ZNF410 motifs completely account for ZNF410's effects on fetal globin repression. CRISPR-Cas9 screen, knockout mouse model (Zfp410), xenotransplantation, gene expression analysis, ChIP-seq Nature genetics High 33859416
2021 CHD4 conceals aberrant CTCF-binding sites embedded in H3K9me3-enriched B2 SINE heterochromatin by regulating chromatin accessibility; CHD4 depletion allows aberrant CTCF recruitment within TADs, disrupting local TAD organization; RNA-binding IDRs of CHD4 are required to prevent this aberrant CTCF binding. CHD4 conditional KO/depletion, ATAC-seq, Hi-C, ChIP-seq, domain deletion analysis in mESCs Molecules and cells Medium 34764232
2022 CHD4 interacts with SMYD1, a striated muscle-restricted histone methyltransferase, in cardiac tissue; CHD4 and SMYD1 co-repress a group of common genes and pathways including glycolysis, response to hypoxia, and angiogenesis in the developing heart. Quantitative proteomics (Co-IP-MS), transcriptomics, ATAC-seq, conditional KO mouse hearts Development (Cambridge, England) Medium 38619323
2023 A de novo CHD4 missense mutation (M202I/M195I in mice) causes augmented affinity of CHD4 protein for endocardial BRG1; this enhanced CHD4M195I-BRG1 interaction prevents derepression of Adamts1 transcription, reducing ADAMTS1-mediated trabeculation termination and causing biventricular hypertrabeculation; administration of ADAMTS1 rescues hypertrabeculation defects. Humanized mouse model, Co-IP with MS, ChIP, transcriptomics, genetic rescue (ADAMTS1 administration), echocardiography Circulation research High 37254794
2022 CHD4 depletion in Ewing sarcoma leads to global increase in DNA accessibility and induction of spontaneous DNA damage, increasing susceptibility to DNA-damaging agents; CHD4 and NuRD co-localize with EWS-FLI1 at enhancers/super-enhancers but CHD4 promotes cell survival through chromatin structure regulation rather than modulating EWS-FLI1 activity. CRISPR/Cas9 inactivation screen, ATAC-seq, ChIP-seq, siRNA knockdown, in vivo xenograft, PARP inhibitor combination Cancer research Medium 37963210
2024 CHD4 acts as a chromatin proof-reading enzyme by promoting nucleosome positioning over GATA3 binding motifs to compete with transcription factor-DNA interaction; CHD4 depletion leads to redistribution of transcription factors to previously unoccupied sites and prevents appropriate chromatin opening during GATA3-induced reprogramming. ATAC-seq, ChIP-seq, siRNA knockdown, cellular reprogramming assay Nucleic acids research Medium 38281186
2016 CHD4 represses Wnt signaling in vascular endothelial cells; endothelial deletion of Chd4 upregulates Wnt-responsive transcription factor Tcf7 and Wnt target genes including Pitx2; BRG1 and CHD4 antagonistically modulate Wnt signaling in developing yolk sac vessels. Conditional knockout mouse models (single and double KO), gene expression analysis, Wnt target gene analysis, pharmacological rescue (LiCl) Molecular and cellular biology Medium 22290435
2013 CHD4/NuRD directly binds the promoter of rDNA transcription silencer TIP5 and negatively regulates TIP5 expression, thereby inhibiting rDNA methylation and maintaining demethylated state of rDNA promoters; CHD4/NuRD controls rDNA methylation status through cross-talk with the NoRC complex. ChIP, siRNA knockdown, DNA methylation analysis, gene expression analysis Biochemical and biophysical research communications Medium 23796711
2007 In Xenopus, CHD4/Mi-2beta controls the neuroectoderm/mesoderm boundary by suppressing Sip1 transcription through direct binding to the 5' end of the Sip1 gene body; CHD4/Sip1 epistasis determines the ON threshold for Nodal-dependent Xbra transcription. Gain and loss of CHD4 function in Xenopus embryos, ChIP, epistasis analysis, gene expression analysis Genes & development High 17438000
2024 DNA damage increases N6-methyladenosine (m6A) marks on the lncRNA NEAT1, promoting its accumulation at promoter-associated DSBs; NEAT1 releases CHD4 from NEAT1 at DSBs to fine-tune histone acetylation; this genome-protective role of NEAT1 requires the RNA methyltransferase METTL3 and involves CHD4 release from NEAT1 to regulate chromatin at damage sites. m6A RNA modification analysis, m6A-seq, NEAT1 depletion, siRNA knockdown, DSB focus formation assay, histone acetylation analysis Genes & development Medium 39362776
2013 Chd4 acts as a corepressor of Sox9 during BMP-2-induced chondrogenesis; Chd4 interacts with Hdac1/2, Kap1, and Cbx1 and binds at the Sox9 promoter (-207/-148 region); let-7a miRNA targets the 3'UTR of Chd4 to promote chondrogenesis. ChIP, nuclease hypersensitivity assay, Co-IP (inferred from NuRD complex), siRNA knockdown, proteomics Journal of bone and mineral research Medium 23519980
2022 CHD4 interacts with the transcription factor Znf219 in cardiac tissue; Znf219 represses skeletal muscle sarcomeric genes in cardiomyocytes; aberrant expression of skeletal muscle sarcomere proteins in Znf219 knockdown mouse hearts leads to arrhythmias with increased PR interval. Co-immunoprecipitation, in vitro/in vivo knockdown, cardiac phenotyping, gene expression analysis International journal of molecular sciences Medium 36076959
2022 FBXW7 degrades CHD4 protein via ubiquitination; CHD4 promotes nuclear translocation of β-catenin to activate the Wnt/β-catenin pathway; the FBXW7-CHD4-Wnt/β-catenin axis regulates cancer stem cell maintenance in triple-negative breast cancer. Immunoprecipitation-mass spectrometry, ubiquitination assay, Co-IP, western blot, functional assays (sphere formation, invasion), in vivo xenograft Journal of translational medicine Medium 38268032
2023 CHD4/NuRD directly activates transcription of PLS3 (Plastin 3) by binding the PLS3 promoter in an activating manner; CHD4/NuRD activity at the PLS3 promoter is demonstrated by ChIP and dual-luciferase assays; CHD4 expression is co-regulated with PLS3 and DXZ4 macrosatellite copy number. siRNA knockdown, CHD4 overexpression, ChIP, dual-luciferase promoter assay American journal of human genetics Medium 36812914
2019 CHD4 directly binds the Ripk3 promoter in hypoxic endothelial cells to repress Ripk3 transcription and prevent histone acetylation at that promoter; genetic deletion of Chd4 upregulates Ripk3, and concomitant deletion of Ripk3 partially rescues vascular rupture and lethality in Chd4 mutants. Conditional knockout mouse model, ChIP, histone acetylation analysis, genetic epistasis (Chd4/Ripk3 double KO) Cell death and differentiation High 31235857
2021 CHD4 interacts with the GDNF-responsive transcription factor SALL4 in spermatogonia (independent of NuRD) to regulate gene expression controlling spermatogonial stem cell fate decisions; CHD4 loss significantly impairs SSC regenerative capacity with ~50% reduction in colonization. Co-immunoprecipitation, spermatogonial transplantation, scRNA-seq, siRNA knockdown Stem cell reports Medium 33961790
2016 CHD4 directly binds the proximal promoter of Ucp1 and represses thermogenic gene expression in adipocytes; harmine treatment activates the RAC1-MEK-ERK pathway which triggers CHD4 displacement from the Ucp1 promoter through ERK-mediated post-translational modification of CHD4. ChIP, post-translational modification analysis, siRNA knockdown, pharmacological treatment, reporter assay Scientific reports Medium 27805061
2019 CHD4 loss in mature B cells impairs class switch recombination by reducing AID (activation-induced cytidine deaminase) targeting to the Igh locus; CHD4 directly binds H3K9me3 at the Igh locus and is required for optimal AID recruitment; CHD4 also represses p53 to promote B cell proliferation. Conditional knockout mouse model, ChIP (H3K9me3), flow cytometry (CSR assay), gene expression analysis Cell reports Medium 31042474
2022 CHD4 promotes the interaction between ERK1/2 and MEK1/2, resulting in continuous activation of the MEK/ERK pathway; CHD4 mediates drug efflux to reduce intracellular cisplatin concentration; CHD4 physically interacts with ERK1/2 and MEK1/2 in gastric cancer cells. Immunoprecipitation, proximity ligation assay, LC-MS, western blot, drug sensitivity assay, xenograft Drug resistance updates Low 36603431
2018 CHD4 mutations R975H and R1162W reduce CHD4 protein stability, phenocopying CHD4 depletion to increase cancer stem cell marker CD133 expression; mutant CHD4 activates TGFβ signaling to promote stemness; mutant CHD4 does not impair NuRD complex formation. Genetic engineering, Co-IP (NuRD complex), western blot (protein stability), sphere formation, in vivo tumorigenicity, TGFβ inhibitor treatment American journal of cancer research Medium 29888111
2022 CHD4 mediates SOX2 transcriptional repression by binding the SOX2 promoter in a TRPS1-dependent manner; CHD4 requires TRPS1 for promoter occupancy, and TRPS1 abolishes CHD4-mediated transcriptional activation of SOX2 in luminal breast cancer. ChIP, Co-IP, siRNA knockdown, reporter assay Cellular signalling Low 36075559

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 301 20693977
2010 The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage. The Journal of cell biology 190 20805324
2017 CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes. Cancer cell 157 28486105
2018 Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes. Nature 156 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 134 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 112 27616479
2014 ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state. Cell reports 100 24440720
2018 lncRNA PAPAS tethered to the rDNA enhancer recruits hypophosphorylated CHD4/NuRD to repress rRNA synthesis at elevated temperatures. Genes & development 97 29907651
2006 NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex. The Journal of biological chemistry 97 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 95 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 92 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 87 22219182
2010 The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea. Development (Cambridge, England) 86 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 79 26095183
1999 Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4. Biochemistry 78 10545197
2020 SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair. Nucleic acids research 75 31970415
2020 ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. Molecular cell 75 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 Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations. eLife 70 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 67 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 63 30122475
2021 ZNF410 represses fetal globin by singular control of CHD4. Nature genetics 62 33859416
2016 CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex. The Journal of biological chemistry 62 27235397
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 59 29733391
2016 The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis. Cell metabolism 56 27166947
2020 Chd4 choreographs self-antigen expression for central immune tolerance. Nature immunology 54 32601470
2015 Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation. Blood 54 26265695
2020 CHD4 Promotes Breast Cancer Progression as a Coactivator of Hypoxia-Inducible Factors. Cancer research 52 32699137
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 52 31474762
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 49 26565020
2020 The chromatin remodeling enzyme Chd4 regulates genome architecture in the mouse brain. Nature communications 48 32647123
2016 Helicase CHD4 is an epigenetic coregulator of PAX3-FOXO1 in alveolar rhabdomyosarcoma. The Journal of clinical investigation 48 27760049
2020 NuRD subunit CHD4 regulates super-enhancer accessibility in rhabdomyosarcoma and represents a general tumor dependency. eLife 47 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 43 29891665
2012 MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes. Molecular and cellular biology 42 23071088
2022 KSHV episome tethering sites on host chromosomes and regulation of latency-lytic switch by CHD4. Cell reports 40 35545047
2020 CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A. BMC cancer 37 32228507
2015 Acetyltransferase p300 collaborates with chromodomain helicase DNA-binding protein 4 (CHD4) to facilitate DNA double-strand break repair. Mutagenesis 37 26546801
2022 CHD4 is recruited by GATA4 and NKX2-5 to repress noncardiac gene programs in the developing heart. Genes & development 36 35450884
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
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
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 34 36603431
2019 CHD4 regulates the DNA damage response and RAD51 expression in glioblastoma. Scientific reports 34 30872624
2023 Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies. Annals of the rheumatic diseases 33 37130727
2011 ATM mediated phosphorylation of CHD4 contributes to genome maintenance. Genome integrity 33 21219611
2018 CHD4-mediated loss of E-cadherin determines metastatic ability in triple-negative breast cancer cells. Experimental cell research 32 29305962
2018 CHD4 mutations promote endometrial cancer stemness by activating TGF-beta signaling. American journal of cancer research 29 29888111
2012 Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4. FEBS letters 29 22749909
2016 CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity. The Journal of clinical investigation 28 27140400
2020 CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation. Nature communications 27 32251276
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 23 30967373
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 21 34161330
2022 Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development. Epigenetics & chromatin 19 35568926
2021 CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells. International journal of molecular sciences 18 33419089
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 CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer. International journal of biological sciences 17 33994851
2021 A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool. Stem cell reports 16 33961790
2021 Role of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Cancer. Frontiers in oncology 16 33981601
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
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 16 23519980
2024 CHD4 R975H mutant activates tumorigenic pathways and promotes stemness and M2-like macrophage polarization in endometrial cancer. Scientific reports 15 39127769
2023 Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1. Circulation research 15 37254794
2022 ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers. BMC biology 15 36153585
2024 NEAT1 promotes genome stability via m6A methylation-dependent regulation of CHD4. Genes & development 14 39362776
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 14 36681835
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 14 30409903
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 The Chromatin Remodeler CHD4 Sustains Ewing Sarcoma Cell Survival by Controlling Global Chromatin Architecture. Cancer research 13 37963210
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
2024 CHD4 and SMYD1 repress common transcriptional programs in the developing heart. Development (Cambridge, England) 13 38619323
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
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
2021 CHD4 Conceals Aberrant CTCF-Binding Sites at TAD Interiors by Regulating Chromatin Accessibility in Mouse Embryonic Stem Cells. Molecules and cells 11 34764232
2007 CHD4/Mi-2beta activity is required for the positioning of the mesoderm/neuroectoderm boundary in Xenopus. Genes & development 11 17438000
2022 RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodeling. Cell reports 10 35649367
2022 CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice†. Biology of reproduction 10 35980806
2022 Interplay between the Chd4/NuRD Complex and the Transcription Factor Znf219 Controls Cardiac Cell Identity. International journal of molecular sciences 10 36076959
2022 The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families. Nature communications 10 36473839
2021 Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination. Immunological reviews 10 34927255
2024 Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4. Nucleic acids research 9 38281186
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
2019 The Tale of CHD4 in DNA Damage Response and Chemotherapeutic Response. Journal of cancer research and cellular therapeutics 9 32577620
2022 CHD4 mediates SOX2 transcription through TRPS1 in luminal breast cancer. Cellular signalling 8 36075559

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