Tumor hypoxia causes DNA hypermethylation by reducing TET activity

  title={Tumor hypoxia causes DNA hypermethylation by reducing TET activity},
  author={Bernard Thienpont and Jessica Steinbacher and Hui Zhao and Flora D’Anna and Anna Kuchnio and Athanasios Ploumakis and Bart Ghesqui{\`e}re and Laurien Van Dyck and Bram Boeckx and Luc Schoonjans and Els Hermans and Fr{\'e}d{\'e}ric Amant and Vessela N. Kristensen and Kian Peng Koh and Massimiliano Mazzone and Mathew L Coleman and Thomas Carell and Peter Carmeliet and Diether Lambrechts},
Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in… CONTINUE READING
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