ArticleNucleic acids research2019
DNMT3L facilitates DNA methylation partly by maintaining DNMT3A stability in mouse embryonic stem cells.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 174 citations in OpenAlex.
- Mammalian DNA methyltransferases in DNA methylation and imprinted gene expression in extraembryonic ectoderm of post-implantation embryos.The Journal of biological chemistry · 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
- Epigenetic blind spots - the role of DNA methylation dynamics in stem cell-based models of embryogenesis.FEBS letters · 2026Article
- Functional characterization of UHRF1 variants in facilitating DNA methylation.The Journal of biological chemistry · 2026Article
- Newly identified invasion drivers define the tumor front in oral squamous cell carcinoma.Cell death discovery · 2026Article
- Mechanisms of DNA methyltransferase 3A1-mediated DNA methylation of nucleosomes.The Journal of biological chemistry · 2026Article
- Epigenetic Regulation of Production Traits in Ruminants: Implications for Breeding and Selection.Biology · 2026Review
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- Uncovering the acetylation sites of Dnmt3L that regulate protein stability and differentiation potency in embryonic stem cells.Experimental & molecular medicine · 2026Article
- Structural insight into hierarchical DNMT3A autoinhibition and its dysregulation in disease.Nature communications · 2026Article
- DNA Methylation in the Ovary and Uterus of Mammalian Animal Models: Implications for Reproductive Function.Genes · 2026Review
- Mechanisms of DNMT3A-3L-mediated de novo DNA methylation on chromatin.Nature structural & molecular biology · 2026Article
- Epigenetic Landscapes in Ulcerative Colitis: From Mechanistic Insights to Clinical Translation.ACS omega · 2025Review
- The epigenetic regulatory network of long noncoding RNAs in hepatocellular carcinoma.Genes & diseases · 2025Review
- The Crucial Role of Epigenetic Modifications in Wharton's Jelly Stem Cells.International journal of molecular sciences · 2025Review
- Epigenetic drugs in cancer therapy.Cancer metastasis reviews · 2025Review
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
- C/EBPβ-Lin28a positive feedback loop triggered by C/EBPβ hypomethylation enhances the proliferation and migration of vascular smooth muscle cells in restenosis.Chinese medical journal · 2025Article
- Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.Nucleic acids research · 2025Article
- An Insight into Differentially Expressed Genes and MicroRNAs in the Pituitary Glands of the Two Estrous Phases of Sheep with DifferentAnimals : an open access journal from MDPI · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
DNMT3L (DNMT3-like), a member of the DNMT3 family, has no DNA methyltransferase activity but regulates de novo DNA methylation. While biochemical studies show that DNMT3L is capable of interacting with both DNMT3A and DNMT3B and stimulating their enzymatic activities, genetic evidence suggests that DNMT3L is essential for DNMT3A-mediated de novo methylation in germ cells but is dispensable for de novo methylation during embryogenesis, which is mainly mediated by DNMT3B. How DNMT3L regulates DNA methylation and what determines its functional specificity are not well understood. Here we show that DNMT3L-deficient mouse embryonic stem cells (mESCs) exhibit downregulation of DNMT3A, especially DNMT3A2, the predominant DNMT3A isoform in mESCs. DNA methylation analysis of DNMT3L-deficient mESCs reveals hypomethylation at many DNMT3A target regions. These results confirm that DNMT3L is a positive regulator of DNA methylation, contrary to a previous report that, in mESCs, DNMT3L regulates DNA methylation positively or negatively, depending on genomic regions. Mechanistically, DNMT3L forms a complex with DNMT3A2 and prevents DNMT3A2 from being degraded. Restoring the DNMT3A protein level in DNMT3L-deficient mESCs partially recovers DNA methylation. Thus, our work uncovers a role for DNMT3L in maintaining DNMT3A stability, which contributes to the effect of DNMT3L on DNMT3A-dependent DNA methylation.
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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.