Skip to main content

Thank you for visiting nature.com. 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.

Keeping methylation at bay

Nature Genetics volume 47, pages 427–428 (2015)Cite this article

Subjects

A hallmark of CpG islands is their unmethylated state, and determining how DNA methylation can invade these elements is therefore important for understanding developmental gene regulation and disease. A new study shows that FBXL10, a protein commonly altered by mutation in leukemia, is part of a mechanism that blocks methylation of CpG islands.

Since their discovery over 30 years ago, CpG islands have become important beacons in the landscape of the mammalian genome. These GC-rich sequence elements demarcate a large fraction of gene promoters and, in stark contrast to the bulk of the genome, are sites of unmethylated DNA1. Methylation of CpG islands is associated with long-term gene silencing and occurs normally in a small number of CpG islands, such as those on the inactive X chromosome in female cells, the control regions of imprinted genes and the promoters of germ cell–expressed genes in somatic cells2. Aberrant CpG island methylation occurs in cancer. Despite this long history, the mechanisms by which CpG islands are protected against or become prone to DNA methylation are not yet fully understood. On page 477 of this issue, Tim Bestor and colleagues now identify a protein, FBXL10, that binds CpG islands universally and serves to protect a specific subset from acquiring DNA methylation3.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: FBXL10 is bound at CpG islands as part of the variant PRC1 complex (vPRC1).

References

  1. Deaton, A.M. & Bird, A. Genes Dev. 25, 1010–1022 (2011).

    Article  CAS  Google Scholar 

  2. Auclair, G., Guibert, S., Bender, A. & Weber, M. Genome Biol. 15, 545 (2014).

    Article  Google Scholar 

  3. Boulard, M., Edwards, J.R. & Bestor, T.H. Nat. Genet. 47, 477–483 (2015).

    Article  Google Scholar 

  4. Voigt, P., Tee, W.W. & Reinberg, D. Genes Dev. 27, 1318–1338 (2013).

    Article  CAS  Google Scholar 

  5. Klose, R.J., Cooper, S., Farcas, A.M., Blackledge, N.P. & Brockdorff, N. PLoS Genet. 9, e1003717 (2013).

    Article  CAS  Google Scholar 

  6. He, J., Kallin, E.M., Tsukada, Y. & Zhang, Y. Nat. Struct. Mol. Biol. 15, 1169–1175 (2008).

    Article  CAS  Google Scholar 

  7. Farcas, A.M. et al. eLife 1, e00205 (2012).

    Article  Google Scholar 

  8. Wu, X., Johansen, J.V. & Helin, K. Mol. Cell 49, 1134–1146 (2013).

    Article  CAS  Google Scholar 

  9. Blackledge, N.P. et al. Cell 157, 1445–1459 (2014).

    Article  CAS  Google Scholar 

  10. Riising, E.M. et al. Mol. Cell 55, 347–360 (2014).

    Article  CAS  Google Scholar 

  11. Fukuda, T., Tokunaga, A., Sakamoto, R. & Yoshida, N. Mol. Cell. Neurosci. 46, 614–624 (2011).

    Article  CAS  Google Scholar 

  12. Viré, E. et al. Nature 439, 871–874 (2006).

    Article  Google Scholar 

  13. Neri, F. et al. Cell 155, 121–134 (2013).

    Article  CAS  Google Scholar 

  14. Baubec, T. et al. Nature 520, 243–247 (2015).

    Article  CAS  Google Scholar 

  15. Pasqualucci, L. et al. Nat. Genet. 43, 830–837 (2011).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gavin Kelsey is in the Epigenetics Programme, Babraham Institute, Cambridge, UK, and at the Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.,

    Gavin Kelsey

Authors
  1. Gavin Kelsey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gavin Kelsey.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kelsey, G. Keeping methylation at bay. Nat Genet 47, 427–428 (2015). https://doi.org/10.1038/ng.3290

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.3290

This article is cited by

Search

Advanced search

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