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Oxidative and non-oxidative active turnover of genomic methylcytosine in distinct pluripotent states

View ORCID ProfileFabio Spada, View ORCID ProfileSarah Schiffers, View ORCID ProfileAngie Kirchner, View ORCID ProfileYingqian Zhang, Olesea Kosmatchev, Eva Korytiakova, View ORCID ProfileRené Rahimoff, Charlotte Ebert, View ORCID ProfileThomas Carell
doi: https://doi.org/10.1101/846584
Fabio Spada
1M
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  • For correspondence: fabio.spada@cup.lmu.de Thomas.Carell@cup.lmu.de
Sarah Schiffers
1M
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Angie Kirchner
1M
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Yingqian Zhang
1M
2College of Chemisty, State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, Nankai University, Tianjin, China
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Olesea Kosmatchev
1M
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Eva Korytiakova
1M
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René Rahimoff
1M
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Charlotte Ebert
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Thomas Carell
1M
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  • For correspondence: fabio.spada@cup.lmu.de Thomas.Carell@cup.lmu.de
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Abstract

Epigenetic plasticity underpins cell potency, but the extent to which active turnover of DNA methylation contributes to such plasticity is not known and the underlying pathways are poorly understood. Here we use mass spectrometry in combination with isoptope tracing to quantitatively address the global turnover of genomic methylcytidine (mdC), hydroxymethylcytidine (hmdC) and formylcytidine (fdC) across mouse pluripotent cell states. High rates of mdC/hmdC oxidation and fdC turnover characterize a formative-like pluripotent state. In primed pluripotent cells the global mdC turnover rate is about 3-6% faster than can be explained by passive dilution through DNA synthesis. While this active component is largely dependent on Tet-mediated mdC oxidation, we also unveiled an additional mdC oxidation-independent turnover process based on DNA repair. This process accelerates upon acquisition of primed pluripotency and returns to low levels in lineage committed cells. Thus, in pluripotent cells active mdC turnover involves both mdC oxidation-dependent and -independent processes.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 18, 2019.
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Oxidative and non-oxidative active turnover of genomic methylcytosine in distinct pluripotent states
Fabio Spada, Sarah Schiffers, Angie Kirchner, Yingqian Zhang, Olesea Kosmatchev, Eva Korytiakova, René Rahimoff, Charlotte Ebert, Thomas Carell
bioRxiv 846584; doi: https://doi.org/10.1101/846584
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Oxidative and non-oxidative active turnover of genomic methylcytosine in distinct pluripotent states
Fabio Spada, Sarah Schiffers, Angie Kirchner, Yingqian Zhang, Olesea Kosmatchev, Eva Korytiakova, René Rahimoff, Charlotte Ebert, Thomas Carell
bioRxiv 846584; doi: https://doi.org/10.1101/846584

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