ArticleScientific reports2020
Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 18 citations in OpenAlex.
- Abasic site repair in APE1-deficient mouse embryonic stem cells: a matter for the MRN complex and ATM signaling.Nucleic acids research · 2026Article
- DREAMS illuminates spatial DNA and RNA modification landscapes.Nature cell biology · 2026Article
- PARP1 inhibition in naïve mouse embryonic stem cells induces viral mimicry.Nucleic acids research · 2026Article
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- Article
- Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation.Nature communications · 2024Article
- The epigenetic modification of DNA methylation in neurological diseases.Frontiers in immunology · 2024Review
- Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components.Nucleic acids research · 2023Article
- TET1 regulates gene expression and repression of endogenous retroviruses independent of DNA demethylation.Nucleic acids research · 2022Article
- Spectroscopic and in vitro Investigations of FeChembiochem : a European journal of chemical biology · 2022Review
- Small Molecule Inhibitors of TET Dioxygenases: Bobcat339 Activity Is Mediated by Contaminating Copper(II).ACS medicinal chemistry letters · 2022Article
- Tet enzymes are essential for early embryogenesis and completion of embryonic genome activation.EMBO reports · 2022Article
- Structure and Function of TET Enzymes.Advances in experimental medicine and biology · 2022Article
- The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response.Scientific reports · 2021Article
- Deformylation of 5-Formylcytidine in Different Cell Types.Angewandte Chemie (International ed. in English) · 2021Article
- Downregulation of 5-hydroxymethylcytosine is an early event in pancreatic tumorigenesis.The Journal of pathology · 2021Article
- The Complexity of TET2 Functions in Pluripotency and Development.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosine DNA bases can be methylated by DNA methyltransferases and subsequently oxidized by TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are considered demethylation intermediates as well as stable epigenetic marks. To dissect the contributions of these cytosine modifying enzymes, we generated combinations of Tet knockout (KO) embryonic stem cells (ESCs) and systematically measured protein and DNA modification levels at the transition from naive to primed pluripotency. Whereas the increase of genomic 5-methylcytosine (5mC) levels during exit from pluripotency correlated with an upregulation of the de novo DNA methyltransferases DNMT3A and DNMT3B, the subsequent oxidation steps turned out to be far more complex. The strong increase of oxidized cytosine bases (5hmC, 5fC, and 5caC) was accompanied by a drop in TET2 levels, yet the analysis of KO cells suggested that TET2 is responsible for most 5fC formation. The comparison of modified cytosine and enzyme levels in Tet KO cells revealed distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation arguing against a processive mechanism of 5mC oxidation. The apparent independent steps of 5hmC and 5fC formation suggest yet to be identified mechanisms regulating TET activity that may constitute another layer of epigenetic regulation.
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