ArticleNucleic acids research2021
Flanking sequence preference modulates de novo DNA methylation in the mouse genome.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- Chromatin binding and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation.Genes & development · 2026Article
- A tunable, ultrasensitive threshold in enzymatic activity governs the DNA methylation landscape.Biophysical journal · 2026Article
- Epigenetic motifs distinguishing endogenous from exogenous retroviral integrants.Journal of virology · 2025Article
- DNA methylation biomarkers for the diagnosis and treatment management of breast cancer: where are we now?Epigenomics · 2025Review
- So close yet so far apart: distinct flanking sequence recognition by DNMT3A and DNMT3B.Communications biology · 2025Article
- Article
- The N-terminal region of DNMT3A engages the nucleosome surface to aid chromatin recruitment.EMBO reports · 2024Article
- Using human disease mutations to understand de novo DNA methyltransferase function.Biochemical Society transactions · 2024Review
- DNMT3B overexpression downregulates genes with CpG islands, common motifs, and transcription factor binding sites that interact with DNMT3B.Scientific reports · 2022Article
- DNA sequence and chromatin modifiers cooperate to confer epigenetic bistability at imprinting control regions.Nature genetics · 2022Article
- Local CpG density affects the trajectory and variance of age-associated DNA methylation changes.Genome biology · 2022Article
- Mediating and maintaining methylation while minimizing mutation: Recent advances on mammalian DNA methyltransferases.Current opinion in structural biology · 2022Review
- 5-methylcytosine turnover: Mechanisms and therapeutic implications in cancer.Frontiers in molecular biosciences · 2022Review
- Enzymology of Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- The interplay between DNA and histone methylation: molecular mechanisms and disease implications.EMBO reports · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian de novo DNA methyltransferases (DNMT) are responsible for the establishment of cell-type-specific DNA methylation in healthy and diseased tissues. Through genome-wide analysis of de novo methylation activity in murine stem cells we uncover that DNMT3A prefers to methylate CpGs followed by cytosines or thymines, while DNMT3B predominantly methylates CpGs followed by guanines or adenines. These signatures are further observed at non-CpG sites, resembling methylation context observed in specialised cell types, including neurons and oocytes. We further show that these preferences result from structural differences in the catalytic domains of the two de novo DNMTs and are not a consequence of differential recruitment to the genome. Molecular dynamics simulations suggest that, in case of human DNMT3A, the preference is due to favourable polar interactions between the flexible Arg836 side chain and the guanine that base-pairs with the cytosine following the CpG. By exchanging arginine to a lysine, the corresponding side chain in DNMT3B, the sequence preference is reversed, confirming the requirement for arginine at this position. This context-dependent enzymatic activity provides additional insights into the complex regulation of DNA methylation patterns.
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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.