ArticleProceedings of the National Academy of Sciences of the United States of America2015
Biochemical characterization of a Naegleria TET-like oxygenase and its application in single molecule sequencing of 5-methylcytosine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Repressive Cytosine Methylation is a Marker of Viral Gene Transfer Across Divergent Eukaryotes.Molecular biology and evolution · 2025Article
- Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unravelling 2-oxoglutarate turnover and substrate oxidation dynamics in 5-methylcytosine-oxidising TET enzymes.Communications chemistry · 2024Article
- Characterization of the enzyme for 5-hydroxymethyluridine production and its role in silencing transposable elements in dinoflagellates.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications.PLoS genetics · 2024Article
- Modular Oxidation of Cytosine Modifications and Their Application in Direct and Quantitative Sequencing of 5-Hydroxymethylcytosine.Journal of the American Chemical Society · 2023Article
- Dynamic changes in genomic 5-hydroxymethyluracil and N6-methyladenine levels in the Drosophila melanogaster life cycle and in response to different temperature conditions.Scientific reports · 2022Article
- Chemical and enzymatic modifications of 5-methylcytosine at the intersection of DNA damage, repair, and epigenetic reprogramming.PloS one · 2022Article
- Recent Advances on DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications.Advances in experimental medicine and biology · 2022Article
- Phage-encoded ten-eleven translocation dioxygenase (TET) is active in C5-cytosine hypermodification in DNA.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- TET-TDG Active DNA Demethylation at CpG and Non-CpG Sites.Journal of molecular biology · 2021Article
- Enzymatic Hydroxylation and Excision of Extended 5-Methylcytosine Analogues.Journal of molecular biology · 2020Article
- Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution.Nature biotechnology · 2019Article
- Structural basis for effects of CpA modifications on C/EBPβ binding of DNA.Nucleic acids research · 2019Article
- Bisulfite-free and base-resolution analysis of 5-methylcytidine and 5-hydroxymethylcytidine in RNA with peroxotungstate.Chemical communications (Cambridge, England) · 2019Article
- Detecting and interpreting DNA methylation marks.Current opinion in structural biology · 2018Review
- Highly Selective 5-Formyluracil Labeling and Genome-wide Mapping Using (2-Benzimidazolyl)Acetonitrile Probe.iScience · 2018Article
- Sequencing 5-Hydroxymethyluracil at Single-Base Resolution.Angewandte Chemie (International ed. in English) · 2018Article
- Synthesis and biophysical analysis of modified thymine-containing DNA oligonucleotides.Chemical communications (Cambridge, England) · 2017Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Modified DNA bases in mammalian genomes, such as 5-methylcytosine ((5m)C) and its oxidized forms, are implicated in important epigenetic regulation processes. In human or mouse, successive enzymatic conversion of (5m)C to its oxidized forms is carried out by the ten-eleven translocation (TET) proteins. Previously we reported the structure of a TET-like (5m)C oxygenase (NgTET1) from Naegleria gruberi, a single-celled protist evolutionarily distant from vertebrates. Here we show that NgTET1 is a 5-methylpyrimidine oxygenase, with activity on both (5m)C (major activity) and thymidine (T) (minor activity) in all DNA forms tested, and provide unprecedented evidence for the formation of 5-formyluridine ((5f)U) and 5-carboxyuridine ((5ca)U) in vitro. Mutagenesis studies reveal a delicate balance between choice of (5m)C or T as the preferred substrate. Furthermore, our results suggest substrate preference by NgTET1 to (5m)CpG and TpG dinucleotide sites in DNA. Intriguingly, NgTET1 displays higher T-oxidation activity in vitro than mammalian TET1, supporting a closer evolutionary relationship between NgTET1 and the base J-binding proteins from trypanosomes. Finally, we demonstrate that NgTET1 can be readily used as a tool in (5m)C sequencing technologies such as single molecule, real-time sequencing to map (5m)C in bacterial genomes at base resolution.
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