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5-Formylcytosine can be a stable DNA modification in mammals

Abstract

5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA modification. These results suggest that 5fC has functional roles in DNA that go beyond being a demethylation intermediate.

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Figure 1: Dynamics of global levels of 5fC during mouse development are distinct from those of 5hmC.
Figure 2: 5fC can be a stable DNA modification in vivo.

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Acknowledgements

We thank C. d'Santos and D. Oxley for their support with mass spectrometry and G. Xu for kindly providing TET-TKO mES cells. This work was supported by Cancer Research UK (C14303/A17197, S.B.), The Wellcome Trust (WT099232, S.B.; WT095645/Z/11/Z, W.R.) and the Biotechnology and Biological Sciences Research Council UK (BB/K010867/1, W.R.).

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Authors

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M.B., S.U.-L. and S.B. conceived the study; S.U.-L., M.B., H.E.B. and M.I. performed experiments; M.B. and X.Y. carried out mass spectrometry and data analysis; S.B., A.M. and W.R. supervised the project; M.B. and S.B. wrote the manuscript with contributions from all authors.

Corresponding author

Correspondence to Shankar Balasubramanian.

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Competing interests

S.B. and W.R. are advisors and shareholders of Cambridge Epigenetix, Ltd.

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Supplementary Results, Supplementary Figures 1–9 and Supplementary Table 1 (PDF 922 kb)

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Bachman, M., Uribe-Lewis, S., Yang, X. et al. 5-Formylcytosine can be a stable DNA modification in mammals. Nat Chem Biol 11, 555–557 (2015). https://doi.org/10.1038/nchembio.1848

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