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Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency

By Christopher B. Mulholland, Franziska R Traube, Edris Parsa, Eva-Maria Eckl, Maximillian Schönung, Miha Modic, Michael D. Bartoschek, Paul Stolz, Joel Ryan, Thomas Carell, Heinrich Leonhardt, Sebastian Bultmann

Posted 13 Mar 2018
bioRxiv DOI: 10.1101/281519 (published DOI: 10.1038/s41598-020-68600-3)

The TET-oxidized cytosine derivatives, 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), are considered DNA demethylation intermediates as well as stable epigenetic marks in mammals. We compared modified cytosine and enzyme levels in TET-knockout cells during naive pluripotency exit and found distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation. The divergent modified cytosine levels argue for independent consecutive oxidation steps in vivo with broad implications for epigenetic regulation.

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