학술논문

Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks
BIOCHEMISTRY
Document Type
Author abstract
Clinical report
Source
Proceedings of the National Academy of Sciences of the United States. July 25, 2006, Vol. 103 Issue 30, p11112, 6 p.
Subject
Research
Cytosine -- Research
Methylation -- Research
DNA repair -- Research
Language
English
ISSN
0027-8424
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. DNA repair | epigenetics | transcription | chromatin | glucocorticoids