Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

5-Formylcytosine can be a stable DNA modification in mammals


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

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.


  1. Ooi, S.K., O'Donnell, A.H. & Bestor, T.H. J. Cell Sci. 122, 2787–2791 (2009).

    Article  CAS  Google Scholar 

  2. Goll, M.G. & Bestor, T.H. Annu. Rev. Biochem. 74, 481–514 (2005).

    Article  CAS  Google Scholar 

  3. Kriaucionis, S. & Heintz, N. Science 324, 929–930 (2009).

    Article  CAS  Google Scholar 

  4. Tahiliani, M. et al. Science 324, 930–935 (2009).

    Article  CAS  Google Scholar 

  5. Globisch, D. et al. PLoS ONE 5, e15367 (2010).

    Article  CAS  Google Scholar 

  6. Bachman, M. et al. Nat. Chem. 6, 1049–1055 (2014).

    Article  CAS  Google Scholar 

  7. He, Y.F. et al. Science 333, 1303–1307 (2011).

    Article  CAS  Google Scholar 

  8. Ito, S. et al. Science 333, 1300–1303 (2011).

    Article  CAS  Google Scholar 

  9. Pfaffeneder, T. et al. Nat. Chem. Biol. 10, 574–581 (2014).

    Article  CAS  Google Scholar 

  10. Song, C.X. & He, C. Trends Biochem. Sci. 38, 480–484 (2013).

    Article  CAS  Google Scholar 

  11. Schiesser, S. et al. J. Am. Chem. Soc. 135, 14593–14599 (2013).

    Article  CAS  Google Scholar 

  12. Neri, F. et al. Cell Reports 10, 674–683 (2015).

    Article  CAS  Google Scholar 

  13. Cortázar, D. et al. Nature 470, 419–423 (2011).

    Article  Google Scholar 

  14. Cortellino, S. et al. Cell 146, 67–79 (2011).

    Article  CAS  Google Scholar 

  15. Hu, X. et al. Cell Stem Cell 14, 512–522 (2014).

    Article  CAS  Google Scholar 

  16. Booth, M.J., Marsico, G., Bachman, M., Beraldi, D. & Balasubramanian, S. Nat. Chem. 6, 435–440 (2014).

    Article  CAS  Google Scholar 

  17. Song, C.X. et al. Cell 153, 678–691 (2013).

    Article  CAS  Google Scholar 

  18. Kraus, T.F., Guibourt, V. & Kretzschmar, H.A. J. Neural Transm. 10.1007/s00702-014-1346-4 (4 December 2014).

  19. Iurlaro, M. et al. Genome Biol. 14, R119 (2013).

    Article  Google Scholar 

  20. Spruijt, C.G. et al. Cell 152, 1146–1159 (2013).

    Article  CAS  Google Scholar 

  21. Booth, M.J. et al. Science 336, 934–937 (2012).

    Article  CAS  Google Scholar 

  22. Yu, M. et al. Cell 149, 1368–1380 (2012).

    Article  CAS  Google Scholar 

  23. Lu, X. et al. Cell Res. 25, 386–389 (2015).

    Article  CAS  Google Scholar 

  24. Raiber, E.A. et al. Nat. Struct. Mol. Biol. 22, 44–49 (2015).

    Article  CAS  Google Scholar 

  25. Ying, Q.L. et al. Nature 453, 519–523 (2008).

    Article  CAS  Google Scholar 

Download references


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.).

Author information

Authors and Affiliations



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.

Ethics declarations

Competing interests

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

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing