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Access through your institution Buy or subscribe DNA hypermethylation at promoters, which manifests with an increase in the levels of 5-methylcytosine (5mC), results in transcriptional
repression. In cancer cells, DNA hypermethylation is often concentrated at the promoters of tumour suppressor genes owing to the impairment of demethylation, which occurs by unknown
mechanisms. Thienpont _et al_. now show that oxygen deprivation (hypoxia) promotes DNA hypermethylation by interfering with the activity of ten-eleven translocation methylcytosine
dioxygenases (TETs) — enzymes that are involved in DNA demethylation. The first step of 5mC demethylation involves its TET-mediated oxidation to 5-hydroxymethylcytosine (5hmC). As this step
involves oxygen, the authors reasoned that hypoxia, which is frequently associated with tumour expansion, might be linked to the impairment of DNA demethylation observed in cancer cells.
Indeed, in hypoxic human and murine cell lines, global levels of 5hmC were decreased and this was linked to decreased TET activity resulting from hypoxia. The loss of 5hmC in hypoxic cells
was most prevalent at promoter regions and it was associated with a concomitant increase in the levels of 5mC and a decrease in gene expression from the affected loci. Thus, hypoxia-induced
impairment of TET activity directly translates to DNA hypermethylation with functional consequences for gene expression. Importantly, 5hmC levels were also decreased in cells from hypoxic
regions of human tumours, which suggests that hypoxia drives DNA hypermethylation in cancers _in vivo_. This is a preview of subscription content, access via your institution ACCESS OPTIONS
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institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Thienpont, B. et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. _Nature_
http://dx.doi.org/10.1038/nature19081 (2016) Download references Authors * Paulina Strzyz View author publications You can also search for this author inPubMed Google Scholar RELATED LINKS
RELATED LINKS RELATED LINKS IN NATURE RESEARCH Pastor, W. A., Aravind, L. & Rao, A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. _Nat. Rev.
Mol. Cell Biol._ 14, 341–356 (2013) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Strzyz, P. Hypoxia as an off switch for gene expression. _Nat Rev Mol
Cell Biol_ 17, 610 (2016). https://doi.org/10.1038/nrm.2016.119 Download citation * Published: 01 September 2016 * Issue Date: October 2016 * DOI: https://doi.org/10.1038/nrm.2016.119 SHARE
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