ArticleMolecular cell2022
Selective chemical tracking of Dnmt1 catalytic activity in live cells.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Live-cell DNMT3A "catalysome" mapping using engineered methyl-transfer pathways.Nucleic acids research · 2026Article
- Harnessing Methyltransferase-Guided Targeting for Sequence-Specific Proximity Labeling of DNA.Angewandte Chemie (International ed. in English) · 2026Article
- Selective chemical tracking of DNA methylomes in live cells.Epigenomics · 2025Article
- Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation.Cell · 2025Article
- The genome in space and time comes of age.Nucleus (Austin, Tex.) · 2024Article
- SUPREM: an engineered non-site-specific m6A RNA methyltransferase with highly improved efficiency.Nucleic acids research · 2024Article
- Engineered Methionine Adenosyltransferase Cascades for Metabolic Labeling of Individual DNA Methylomes in Live Cells.Journal of the American Chemical Society · 2024Article
- DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma.Molecular cancer · 2024Article
- Chemical Expansion of the Methyltransferase Reaction: Tools for DNA Labeling and Epigenome Analysis.Accounts of chemical research · 2023Article
- DNA Labeling Using DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzymatic methylation of cytosine to 5-methylcytosine in DNA is a fundamental epigenetic mechanism involved in mammalian development and disease. DNA methylation is brought about by collective action of three AdoMet-dependent DNA methyltransferases, whose catalytic interactions and temporal interplay are poorly understood. We used structure-guided engineering of the Dnmt1 methyltransferase to enable catalytic transfer of azide tags onto DNA from a synthetic cofactor analog, Ado-6-azide, in vitro. We then CRISPR-edited the Dnmt1 locus in mouse embryonic stem cells to install the engineered codon, which, following pulse internalization of the Ado-6-azide cofactor by electroporation, permitted selective azide tagging of Dnmt1-specific genomic targets in cellulo. The deposited covalent tags were exploited as "click" handles for reading adjoining sequences and precise genomic mapping of the methylation sites. The proposed approach, Dnmt-TOP-seq, enables high-resolution temporal tracking of the Dnmt1 catalysis in mammalian cells, paving the way to selective studies of other methylation pathways in eukaryotic systems.
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Registered trials
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.