ArticleNucleic acids research2018
Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Silencing of humanJournal of Huntington's disease · 2026Article
- Early postnatal DNA methylation dynamics define neuronal subtypes and are disrupted by MECP2 loss.bioRxiv : the preprint server for biology · 2026Article
- Choline and DNA methylation: impact across metabolic, oncogenic and neurodevelopmental disorders.Clinical epigenetics · 2026Review
- Scaling and self-similarity in the formation of the embryonic epigenome.Nature physics · 2026Article
- Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain.Scientific reports · 2025Article
- ATRX ADD domain is a versatile module for recognizing macroH2A, H3, and beyond.Acta biochimica et biophysica Sinica · 2025Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Combined and differential roles of ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells.Nature communications · 2024Article
- Molecular signatures in Mendelian neurodevelopment: a focus on ubiquitination driven DNA methylation aberrations.Frontiers in molecular neuroscience · 2024Review
- Methyl-CpG binding protein 2 expression is associated with symptom severity in patients with PTSD in a sex-dependent manner.Translational psychiatry · 2023Article
- Epigenetic and epitranscriptomic regulation of axon regeneration.Molecular psychiatry · 2023Review
- The MECP2-TRD domain interacts with the DNMT3A-ADD domain at the H3-tail binding site.Protein science : a publication of the Protein Society · 2023Article
- A study on DNA methylation modifying natural compounds identified EGCG for induction of IFI16 gene expression related to the innate immune response in cancer cells.Oncology letters · 2022Article
- DNA methylation-independent long-term epigenetic silencing with dCRISPR/Cas9 fusion proteins.Life science alliance · 2022Article
- Enzymology of Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- Proteins That Read DNA Methylation.Advances in experimental medicine and biology · 2022Article
- Transcriptomic and Epigenomic Landscape in Rett Syndrome.Biomolecules · 2021Review
- Genetic impacts on DNA methylation: research findings and future perspectives.Genome biology · 2021Review
- UVR8 interacts with de novo DNA methyltransferase and suppresses DNA methylation in Arabidopsis.Nature plants · 2021Article
- Alterations toCancer research · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite their central importance in mammalian development, the mechanisms that regulate the DNA methylation machinery and thereby the generation of genomic methylation patterns are still poorly understood. Here, we identify the 5mC-binding protein MeCP2 as a direct and strong interactor of DNA methyltransferase 3 (DNMT3) proteins. We mapped the interaction interface to the transcriptional repression domain of MeCP2 and the ADD domain of DNMT3A and find that binding of MeCP2 strongly inhibits the activity of DNMT3A in vitro. This effect was reinforced by cellular studies where a global reduction of DNA methylation levels was observed after overexpression of MeCP2 in human cells. By engineering conformationally locked DNMT3A variants as novel tools to study the allosteric regulation of this enzyme, we show that MeCP2 stabilizes the closed, autoinhibitory conformation of DNMT3A. Interestingly, the interaction with MeCP2 and its resulting inhibition were relieved by the binding of K4 unmodified histone H3 N-terminal tail to the DNMT3A-ADD domain. Taken together, our data indicate that the localization and activity of DNMT3A are under the combined control of MeCP2 and H3 tail modifications where, depending on the modification status of the H3 tail at the binding sites, MeCP2 can act as either a repressor or activator of 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.