ArticleNucleic acids research2023
On the accuracy of the epigenetic copy machine: comprehensive specificity analysis of the DNMT1 DNA methyltransferase.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- nanoASM: Long-Read Allele-Specific DNA Methylation Profiling Enables Functional Annotation of Regulatory Noncoding Variants in Human Prostate Tissues.bioRxiv : the preprint server for biology · 2026Article
- TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas.Cell reports. Medicine · 2026Article
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- Evolutionary and structural insights into DNMTs and TETs: decoding their functional heterogeneity and oncogenic roles in methylation regulation.BMC molecular and cell biology · 2025Article
- Direct single-nucleotide resolution sequencing of DNA 5-methylcytosine using engineered DNA methyltransferase-mediated CMD-seq.Chemical science · 2025Article
- Dual DNA demethylation mechanisms implement epigenetic memory driven by the pioneer factor PAX7.Science advances · 2025Article
- Advance and challenge of DNA methylation as cancer biomarkers for risk stratification, screening and early detection.Journal of the National Cancer Center · 2025Article
- Systematic analysis of specificities and flanking sequence preferences of bacterial DNA-(cytosine C5)-methyltransferases reveals mechanisms of enzyme- and sequence-specific DNA readout.Nucleic acids research · 2025Article
- Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review).Molecular medicine reports · 2025Review
- Epigenetic gene regulation in plants and its potential applications in crop improvement.Nature reviews. Molecular cell biology · 2025Review
- Specific DNMT3C flanking sequence preferences facilitate methylation of young murine retrotransposons.Communications biology · 2024Article
- Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.Nature communications · 2024Article
- LncRNA HOTTIP promotes LPS-induced lung epithelial cell injury by recruiting DNMT1 to epigenetically regulate SP-C.Journal of cell communication and signaling · 2024Article
- Article
- DNMT1 as an environmental sensor: epigenetic pathways linking environmental exposures, sex hormone signaling, and vulnerability to neurodevelopmental and neurodegenerative diseases.Frontiers in neurologyReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The specificity of DNMT1 for hemimethylated DNA is a central feature for the inheritance of DNA methylation. We investigated this property in competitive methylation kinetics using hemimethylated (HM), hemihydroxymethylated (OH) and unmethylated (UM) substrates with single CpG sites in a randomized sequence context. DNMT1 shows a strong flanking sequence dependent HM/UM specificity of 80-fold on average, which is slightly enhanced on long hemimethylated DNA substrates. To explain this strong effect of a single methyl group, we propose a novel model in which the presence of the 5mC methyl group changes the conformation of the DNMT1-DNA complex into an active conformation by steric repulsion. The HM/OH preference is flanking sequence dependent and on average only 13-fold, indicating that passive DNA demethylation by 5hmC generation is not efficient in many flanking contexts. The CXXC domain of DNMT1 has a moderate flanking sequence dependent contribution to HM/UM specificity during DNA association to DNMT1, but not if DNMT1 methylates long DNA molecules in processive methylation mode. Comparison of genomic methylation patterns from mouse ES cell lines with various deletions of DNMTs and TETs with our data revealed that the UM specificity profile is most related to cellular methylation patterns, indicating that de novo methylation activity of DNMT1 shapes the DNA methylome in these cells.
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