ArticleNature genetics2020
Lysine 4 of histone H3.3 is required for embryonic stem cell differentiation, histone enrichment at regulatory regions and transcription accuracy.
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Histone tail mutants: versatile tools for decoding chromatin, development, and disease.Trends in genetics : TIG · 2026Review
- Histone H3.3 ensures cell proliferation and genomic stability during myeloid cell development.iScience · 2026Article
- ASF1B promotes erythropoiesis by regulating the establishment and enrichment of H3.3 nucleosomes.Nucleic acids research · 2026Article
- The H3K36me3 methyltransferase SETD2 contributes to PAF1C interactions with RNA Pol II and is required for neuronal differentiation.The EMBO journal · 2026Article
- Division of labor among H3K4 methyltransferases defines distinct facets of homeostatic plasticity.Cell reports · 2025Article
- Single amino acid mutations in histone H3.3 illuminate the functional significance of H3K4 methylation in plants.Nature communications · 2025Article
- Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders.iScience · 2025Review
- Histone H3.3 lysine 9 and 27 control repressive chromatin at cryptic enhancers and bivalent promoters.Nature communications · 2024Article
- Plasma cell differentiation is regulated by the expression of histone variant H3.3.Nature communications · 2024Article
- Lipotype acquisition during neural development is not recapitulated in stem cell-derived neurons.Life science alliance · 2024Article
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
- HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.Experimental & molecular medicine · 2024Review
- Role of H3K4 monomethylation in gene regulation.Current opinion in genetics & development · 2024Review
- Functional Roles of H3K4 Methylation in Transcriptional Regulation.Molecular and cellular biology · 2024Review
- Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells.Nature communications · 2023Article
- H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cells.Genome biology · 2023Article
- Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation.Epigenetics & chromatin · 2023Article
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers.BMC biology · 2022Article
- Histone post-translational modifications - cause and consequence of genome function.Nature reviews. Genetics · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in enzymes that modify histone H3 at lysine 4 (H3K4) or lysine 36 (H3K36) have been linked to human disease, yet the role of these residues in mammals is unclear. We mutated K4 or K36 to alanine in the histone variant H3.3 and showed that the K4A mutation in mouse embryonic stem cells (ESCs) impaired differentiation and induced widespread gene expression changes. K4A resulted in substantial H3.3 depletion, especially at ESC promoters; it was accompanied by reduced remodeler binding and increased RNA polymerase II (Pol II) activity. Regulatory regions depleted of H3.3K4A showed histone modification alterations and changes in enhancer activity that correlated with gene expression. In contrast, the K36A mutation did not alter H3.3 deposition and affected gene expression at the later stages of differentiation. Thus, H3K4 is required for nucleosome deposition, histone turnover and chromatin remodeler binding at regulatory regions, where tight regulation of Pol II activity is necessary for proper ESC differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.