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.

authors

Kress C,Thomassin H,Grange T

doi

10.1073/pnas.0601793103

subject

Has Abstract

pub_date

2006-07-25 00:00:00

pages

11112-7

issue

30

eissn

0027-8424

issn

1091-6490

pii

0601793103

journal_volume

103

pub_type

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