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

Mulholland, C. B.; Traube, F. R.; Parsa, E.; Eckl, E.-M.; Schoenung, M.; Modic, M.; Bartoschek, M. D.; Stolz, P.; Ryan, J.; Carell, T.; Leonhardt, H.; Bultmann, S.

doi:10.1101/281519

bioRxiv · 10.1101/281519

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

Mulholland, C. B.·Traube, F. R.·Parsa, E.·Eckl, E.-M.·Schoenung, M.·Modic, M.·Bartoschek, M. D.·Stolz, P.·Ryan, J.·Carell, T.·Leonhardt, H.·Bultmann, S.

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Abstract

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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Mulholland, C. B., Traube, F. R., Parsa, E., Eckl, E.-M., Schoenung, M., Modic, M., Bartoschek, M. D., Stolz, P., Ryan, J., Carell, T., Leonhardt, H., Bultmann, S.. 2018-03-13. Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency. https://doi.org/10.1101/281519

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