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.

  • Research Highlight
  • Published:

METABOLISM AND CANCER

A sugar rush of DNA methylation

Nature Reviews Molecular Cell Biology volume 19, page 617 (2018)Cite this article

Subjects

Access through your institution
Buy or subscribe

DNA cytosine methylation (5mC) is an epigenetic mark that silences gene expression. This mark can be removed by demethylation, the first step of which involves oxidation of 5mC to hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) family of dioxygenases. Notably, both 5mC and 5hmC signatures are frequently deregulated in cancer. Analysis of peripheral blood mononuclear cells (PBMCs) derived from healthy and diabetic individuals revealed that diabetes is associated with a decrease in 5hmC levels. Experiments using PBMCs and other human cell lines confirmed that high glucose conditions are sufficient to reduce global 5hmC levels. They also revealed the concomitant decrease of TET2 protein, indicating that high glucose downregulates TET2 protein levels, leading to reduced 5hmC levels on DNA.

Next, the authors analysed genomic regions that are differentially 5-hydroxymethylated between high and low glucose conditions in a TET2-dependent manner. They used A2058 melanoma cells — which normally have low TET2 and 5hmC levels — in which TET2 was ectopically expressed. TET2 expression was sufficient to raise global 5hmC levels when cells were cultured under normal glucose, and this effect was compromised in high glucose conditions. They identified >30,000 DNA regions that were differentially 5-hydroxymethylated, the majority of which showed a decrease in 5hmC in high glucose conditions. The majority of the identified regions were localized within genes, and gene ontology analysis revealed strong association of these genes with cancer-related pathways. Accordingly, several tumour suppressors were downregulated and several tumour-promoting genes were upregulated when TET2-expressing cells were cultured in high glucose conditions. This indicates that high levels of glucose interfere with DNA demethylation by TET2, which has an impact on the expression of cancer-associated genes.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

References

Original article

  • Wu, D. et al. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature 559, 637–641 (2018)

    Article  CAS  Google Scholar 

Further reading

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/

    Paulina Strzyz

Authors
  1. Paulina Strzyz
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Paulina Strzyz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strzyz, P. A sugar rush of DNA methylation. Nat Rev Mol Cell Biol 19, 617 (2018). https://doi.org/10.1038/s41580-018-0051-9

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41580-018-0051-9

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer