ArticleThe Journal of biological chemistry2017
The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Review
- Identifying critical lysines in mammalian histone H3 with high-throughput CRISPR prime editing.Nature genetics · 2026Article
- CHD4 and NKX2.2 Cooperate to Regulate β-Cell Function by Repressing Non-β-Cell Gene Programs.Diabetes · 2026Article
- Hyperactivation of mTORC1 blocks stem cell fate transitions through TFE3-NuRD association.EMBO reports · 2026Article
- How ATP-Dependent Chromatin Remodeling Complexes Regulate Vertebrate Embryonic Development.International journal of molecular sciences · 2026Review
- Article
- CHD4 and NKX2.2 Cooperate to Regulate Beta Cell Function by Repressing Non-Beta Cell Gene Programs.bioRxiv : the preprint server for biology · 2025Article
- The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification.EMBO reports · 2025Article
- Epigenetic Modifications in the Retinal Pigment Epithelium of the Eye During RPE-Related Regeneration or Retinal Diseases in Vertebrates.Biomedicines · 2025Review
- Widespread impact of nucleosome remodelers on transcription at cis-regulatory elements.Cell reports · 2025Article
- Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance and male germ cell survival.Nucleic acids research · 2025Article
- Phosphorylation-mediated disassembly of C-terminal binding protein 2 tetramer impedes epigenetic silencing of pluripotency in mouse embryonic stem cells.Nucleic acids research · 2024Article
- A LANA peptide inhibits tumor growth by inducing CHD4 protein cleavage and triggers cell death.Cell chemical biology · 2024Article
- The chromatin tapestry as a framework for neurodevelopment.Genome research · 2024Review
- ΔNp63 bookmarks and creates an accessible epigenetic environment for TGFβ-induced cancer cell stemness and invasiveness.Cell communication and signaling : CCS · 2024Article
- Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival.bioRxiv : the preprint server for biology · 2024Article
- Article
- Chromodomain helicase DNA binding protein 4 in cell fate decisions.Hearing research · 2023Review
- RBBP4 is an epigenetic barrier for the induced transition of pluripotent stem cells into totipotent 2C-like cells.Nucleic acids research · 2023Article
- Generation of a Well-Characterized Homozygous Chromodomain-Helicase-DNA-Binding Protein 4International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of transcriptional factors and epigenetic modulators. However, the molecular mechanisms underlying the function of these regulators are not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in ESC regulation remains elusive. Here we report that Chd4 is required for the maintenance of ESC self-renewal. RNAi-mediated silencing of Chd4 disrupted self-renewal and up-regulated lineage commitment-associated genes under self-renewal culture conditions. During ESC differentiation in embryoid body formation, we observed significantly stronger induction of differentiation-associated genes in Chd4-deficient cells. The phenotype was different from that caused by the deletion of Mbd3, another subunit of the NuRD complex. Transcriptomic analyses revealed that Chd4 secured ESC identity by controlling the expression of subsets of pluripotency- and differentiation-associated genes. Importantly, Chd4 repressed the transcription of T box protein 3 (Tbx3), a transcription factor with important functions in ESC fate determination. Tbx3 knockdown partially rescued aberrant activation of differentiation-associated genes, especially of endoderm-associated genes, induced by Chd4 depletion. Moreover, we identified an interaction of Chd4 with the histone variant H2A.Z. This variant stabilized Chd4 by inhibiting Chd4 protein degradation through the ubiquitin-proteasome pathway. Collectively, this study identifies the Chd4-Tbx3 axis in controlling ESC fate and a role of H2A.Z in maintaining the stability of Chd4 proteins.
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