ArticleBiochemistry2018
Maintenance DNA Methyltransferase Activity in the Presence of Oxidized Forms of 5-Methylcytosine: Structural Basis for Ten Eleven Translocation-Mediated DNA Demethylation.
Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- Dual DNA demethylation mechanisms implement epigenetic memory driven by the pioneer factor PAX7.Science advances · 2025Article
- Redox-Driven Epigenetic Modifications in Sperm: Unraveling Paternal Influences on Embryo Development and Transgenerational Health.Antioxidants (Basel, Switzerland) · 2025Review
- Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.Developmental cell · 2024Article
- Article
- 5-hydroxymethylcytosines regulate gene expression as a passive DNA demethylation resisting epigenetic mark in proliferative somatic cells.bioRxiv : the preprint server for biology · 2023Article
- Direct enzymatic sequencing of 5-methylcytosine at single-base resolution.Nature chemical biology · 2023Article
- On the accuracy of the epigenetic copy machine: comprehensive specificity analysis of the DNMT1 DNA methyltransferase.Nucleic acids research · 2023Article
- Targeted DNA Demethylation: Vectors, Effectors and Perspectives.Biomedicines · 2023Review
- Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy.Biomedicines · 2023Review
- Small Molecule Inhibitors of TET Dioxygenases: Bobcat339 Activity Is Mediated by Contaminating Copper(II).ACS medicinal chemistry letters · 2022Article
- Protective Effect of Galangin Methylation Modification Based on Cell Imaging on Inflammatory Lung Injury and Its Molecular Mechanism.Contrast media & molecular imaging · 2022Article
- 5-methylcytosine turnover: Mechanisms and therapeutic implications in cancer.Frontiers in molecular biosciences · 2022Review
- DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases.International journal of molecular sciences · 2021Review
- TET-TDG Active DNA Demethylation at CpG and Non-CpG Sites.Journal of molecular biology · 2021Article
- Active DNA demethylation-The epigenetic gatekeeper of development, immunity, and cancer.Advanced genetics (Hoboken, N.J.) · 2021Review
- Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency.Molecular cell · 2021Article
- Nucleobase Modifiers Identify TET Enzymes as Bifunctional DNA Dioxygenases Capable of Direct N-Demethylation.Angewandte Chemie (International ed. in English) · 2020Article
- DNA 5-Methylcytosine-Specific Amplification and Sequencing.Journal of the American Chemical Society · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A precise balance of DNA methylation and demethylation is required for epigenetic control of cell identity, development, and growth. DNA methylation marks are introduced by de novo DNA methyltransferases DNMT3a/b and are maintained throughout cell divisions by DNA methyltransferase 1 (DNMT1), which adds methyl groups to hemimethylated CpG dinucleotides generated during DNA replication. Ten eleven translocation (TET) dioxygenases oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC), a process known to induce DNA demethylation and gene reactivation. In this study, we investigated the catalytic activity of human DNMT1 in the presence of oxidized forms of mC. A mass spectrometry-based assay was employed to study the kinetics of DNMT1-mediated cytosine methylation in CG dinucleotides containing C, mC, hmC, fC, or caC across from the target cytosine. Homology modeling, coupled with molecular dynamics simulations, was used to explore the structural consequences of mC oxidation with regard to the geometry of protein-DNA complexes. The DNMT1 enzymatic activity was strongly affected by the oxidation status of mC, with the catalytic efficiency decreasing in the following order: mC > hmC > fC > caC. Molecular dynamics simulations revealed that DNMT1 forms an unproductive complex with DNA duplexes containing oxidized forms of mC as a consequence of altered interactions of the target recognition domain of the protein with the C-5 substituent on cytosine. Our results provide new structural and mechanistic insight into TET-mediated DNA demethylation.
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