ArticleNucleic acids research2016
An epigenetic switch regulates de novo DNA methylation at a subset of pluripotency gene enhancers during embryonic stem cell differentiation.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Enhancer Trajectories in Lineage Commitment: Regulatory Logic of States and Cooperation.Biomolecules · 2026Review
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments.Communications biology · 2024Article
- The scaffolding function of LSD1 controls DNA methylation in mouse ESCs.Nature communications · 2024Article
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
- Fluorescent Reporter Systems to Investigate Chromatin Effector Proteins in Living Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- LSD1 promotes the egress of hematopoietic stem and progenitor cells into the bloodstream during the endothelial-to-hematopoietic transition.Developmental biology · 2023Article
- Dnmt3bas coordinates transcriptional induction and alternative exon inclusion to promote catalytically active Dnmt3b expression.Cell reports · 2023Article
- A Paternal Methylation Error in the Congenital Hydrocephalic Texas (H-Tx) Rat Is Partially Rescued with Natural Folate Supplements.International journal of molecular sciences · 2023Article
- Integrative analysis reveals histone demethylase LSD1 promotes RNA polymerase II pausing.iScience · 2022Article
- Enhancer methylation dynamics drive core transcriptional regulatory circuitry in pan-cancer.Oncogene · 2022Article
- Epigenetics of neural differentiation: Spotlight on enhancers.Frontiers in cell and developmental biology · 2022Review
- Review
- A functional LSD1 coregulator screen reveals a novel transcriptional regulatory cascade connecting R-loop homeostasis with epigenetic regulation.Nucleic acids research · 2021Article
- Article
- Simplified MethylRAD Sequencing to Detect Changes in DNA Methylation at Enhancer Elements in Differentiating Embryonic Stem Cells.Epigenomes · 2020Article
- Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Regulation of DNA methylation levels in the process of oral mucosal regeneration in a rat oral ulcer model.Histology and histopathology · 2020Article
- Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency.Nature communications · 2020Article
- Oct4-Mediated Inhibition of Lsd1 Activity Promotes the Active and Primed State of Pluripotency Enhancers.Cell reports · 2020Article
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Authors and funding
6 authors.
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Abstract
Coordinated regulation of gene expression that involves activation of lineage specific genes and repression of pluripotency genes drives differentiation of embryonic stem cells (ESC). For complete repression of pluripotency genes during ESC differentiation, chromatin at their enhancers is silenced by the activity of the Lsd1-Mi2/NuRD complex. The mechanism/s that regulate DNA methylation at these enhancers are largely unknown. Here, we investigated the affect of the Lsd1-Mi2/NuRD complex on the dynamic regulatory switch that induces the local interaction of histone tails with the Dnmt3 ATRX-DNMT3-DNMT3L (ADD) domain, thus promoting DNA methylation at the enhancers of a subset of pluripotency genes. This is supported by previous structural studies showing a specific interaction between Dnmt3-ADD domain with H3K4 unmethylated histone tails that is disrupted by histone H3K4 methylation and histone acetylation. Our data suggest that Dnmt3a activity is triggered by Lsd1-Mi2/NuRD-mediated histone deacetylation and demethylation at these pluripotency gene enhancers when they are inactivated during mouse ESC differentiation. Using Dnmt3 knockout ESCs and the inhibitors of Lsd1 and p300 histone modifying enzymes during differentiation of E14Tg2A and ZHBTc4 ESCs, our study systematically reveals this mechanism and establishes that Dnmt3a is both reader and effector of the epigenetic state at these target sites.
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