ArticleNature genetics2022
The disordered N-terminal domain of DNMT3A recognizes H2AK119ub and is required for postnatal development.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 85 citations in OpenAlex.
- Clonal hematopoiesis-associated DNMT3A mutations derepress bivalent Polycomb target genes and enhance macrophage migration.bioRxiv : the preprint server for biology · 2026Article
- Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A progeria syndrome links DNA hypermethylation to age-related pathology.Nature genetics · 2026Article
- Chromatin binding and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation.Genes & development · 2026Article
- Multiomic analysis of clonal development reveals new regulators of leukemic cell growth.Genes & development · 2026Article
- DNMT1 loss leads to hypermethylation of a subset of late replicating domains by DNMT3A.PLoS genetics · 2026Article
- Mechanisms of DNA methyltransferase 3A1-mediated DNA methylation of nucleosomes.The Journal of biological chemistry · 2026Article
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- Structural insight into hierarchical DNMT3A autoinhibition and its dysregulation in disease.Nature communications · 2026Article
- Epigenetic regulation of T cell exhaustion in cancer.Nature reviews. Cancer · 2026Review
- Convergent DNA methylation abnormalities at enhancers and bivalent promoters in human growth disorders.Epigenetics & chromatin · 2025Article
- Dnmt3a2 expression during embryonic development is required for phenotypic stability.Communications biology · 2025Article
- RAD21L1 Is Sufficient and Effective for Reprogramming Human Sertoli Cells to Phenotypic Spermatogonial Stem Cells Through DNA Methylation and Essential for Male Fertility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Polycomb Repressive Complex 1 and USP16 localize to the mitochondrion and influence its function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Requirements for establishment and epigenetic stability of mammalian heterochromatin.Molecular cell · 2025Article
- Evolutionary and structural insights into DNMTs and TETs: decoding their functional heterogeneity and oncogenic roles in methylation regulation.BMC molecular and cell biology · 2025Article
- DNA Methylation in Long-Term Memory.Physiology (Bethesda, Md.) · 2025Review
- Mechanism of cytarabine-induced neurotoxicity.Nature · 2025Article
- PGLYRP2 drives hepatocyte-intrinsic innate immunity by trapping and clearing hepatitis B virus.The Journal of clinical investigation · 2025Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
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15 authors at 4 institutions in 3 countries.
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Abstract
DNA methyltransferase 3a (DNMT3A) plays a crucial role during mammalian development. Two isoforms of DNMT3A are differentially expressed from stem cells to somatic tissues, but their individual functions remain largely uncharacterized. Here we report that the long isoform DNMT3A1, but not the short DNMT3A2, is essential for mouse postnatal development. DNMT3A1 binds to and regulates bivalent neurodevelopmental genes in the brain. Strikingly, Dnmt3a1 knockout perinatal lethality could be partially rescued by DNMT3A1 restoration in the nervous system. We further show that the intrinsically disordered N terminus of DNMT3A1 is required for normal development and DNA methylation at DNMT3A1-enriched regions. Mechanistically, a ubiquitin-interacting motif embedded in a putative α-helix within the N terminus binds to mono-ubiquitinated histone H2AK119, probably mediating recruitment of DNMT3A1 to Polycomb-regulated regions. These data demonstrate an isoform-specific role for DNMT3A1 in mouse postnatal development and reveal the N terminus as a necessary regulatory domain for DNMT3A1 chromatin occupancy and functions in the nervous system.
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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.