ArticleBiochemistry2019
Selectivity and Promiscuity in TET-Mediated Oxidation of 5-Methylcytosine in DNA and RNA.
Article in Biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- Thymine DNA glycosylase binds to R-loops and excises 5-formyl and 5-carboxyl cytosine from DNA/RNA hybrids.The Journal of biological chemistry · 2026Article
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- 5-Formylcytosine is not a prevalent RNA modification in mammalian cells.Nature communications · 2025Article
- Construction of a risk model based on m5C-associated lncRNAs to predict the prognosis in renal cell carcinoma.Medicine · 2025Article
- Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA.Nucleic acids research · 2024Article
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- Focused Screening Identifies Different Sensitivities of Human TET Oxygenases to the Oncometabolite 2-Hydroxyglutarate.Journal of medicinal chemistry · 2024Article
- Computational Investigation of a Series of Small Molecules as Potential Compounds for Lysyl Hydroxylase-2 (LH2) Inhibition.Journal of chemical information and modeling · 2023Article
- The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer.Frontiers in oncology · 2023Review
- Reactivity-dependent profiling of RNA 5-methylcytidine dioxygenases.Nature communications · 2022Article
- The pH-Dependence of the Hydration of 5-Formylcytosine: an Experimental and Theoretical Study.Chembiochem : a European journal of chemical biology · 2022Article
- Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Methylation Game: Epigenetic and Epitranscriptomic Dynamics of 5-Methylcytosine.Frontiers in cell and developmental biology · 2022Review
- An m5C methylation regulator-associated signature predicts prognosis and therapy response in pancreatic cancer.Frontiers in cell and developmental biology · 2022Article
- Structure and Function of TET Enzymes.Advances in experimental medicine and biology · 2022Article
- Computational investigations of selected enzymes from two iron and α-ketoglutarate-dependent families.Physical chemistry chemical physics : PCCP · 2021Review
- DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases.International journal of molecular sciences · 2021Review
- TETology: Epigenetic Mastermind in Action.Applied biochemistry and biotechnology · 2021Review
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Enzymes of the ten-eleven translocation (TET) family add diversity to the repertoire of nucleobase modifications by catalyzing the oxidation of 5-methylcytosine (5mC). TET enzymes were initially found to oxidize 5-methyl-2'-deoxycytidine in genomic DNA, yielding products that contribute to epigenetic regulation in mammalian cells, but have since been found to also oxidize 5-methylcytidine in RNA. Considering the different configurations of single-stranded (ss) and double-stranded (ds) DNA and RNA that coexist in a cell, defining the scope of TET's preferred activity and the mechanisms of substrate selectivity is critical to better understand the enzymes' biological functions. To this end, we have systematically examined the activity of human TET2 on DNA, RNA, and hybrid substrates in vitro. We found that, while ssDNA and ssRNA are well tolerated, TET2 is most proficient at dsDNA oxidation and discriminates strongly against dsRNA. Chimeric and hybrid substrates containing mixed DNA and RNA character helped reveal two main features by which the enzyme discriminates between substrates. First, the identity of the target nucleotide alone is the strongest reactivity determinant, with a preference for 5-methyldeoxycytidine, while both DNA or RNA are relatively tolerated on the rest of the target strand. Second, while a complementary strand is not required for activity, DNA is the preferred partner, and complementary RNA diminishes reactivity. Our biochemical analysis, complemented by molecular dynamics simulations, provides support for an active site optimally configured for dsDNA reactivity but permissive for various nucleic acid configurations, suggesting a broad range of plausible roles for TET-mediated 5mC oxidation in cells.
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