Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks
Abstract
Cytosine methylation at CpG dinucleotides contributes to the epigenetic maintenance of gene silencing. Dynamic reprogramming of DNA methylation patterns is believed to play a key role during development and differentiation in vertebrates. The mechanisms of DNA demethylation remain unclear and controversial. Here, we present a detailed characterization of the demethylation of an endogenous gene in cultured cells. This demethylation is triggered in a regulatory region by a transcriptional activator, the glucocorticoid receptor. We show that DNA demethylation is an active process, occurring independently of DNA replication, and in a distributive manner without concerted demethylation of cytosines on both strands. We demonstrate that the DNA backbone is cleaved 3′ to the methyl cytidine during demethylation, and we suggest that a DNA repair pathway may therefore be involved in this demethylation.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- July 2006
- DOI:
- 10.1073/pnas.0601793103
- Bibcode:
- 2006PNAS..10311112K
- Keywords:
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- BIOLOGICAL SCIENCES / BIOCHEMISTRY