Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks
- 25 July 2006
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 103 (30), 11112-11117
- https://doi.org/10.1073/pnas.0601793103
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.Keywords
This publication has 90 references indexed in Scilit:
- Intrinsic disorder in scaffold proteins: Getting more from lessProgress in Biophysics and Molecular Biology, 2008
- Mining α-Helix-Forming Molecular Recognition Features with Cross Species Sequence AlignmentsBiochemistry, 2007
- Prediction of kinase‐specific phosphorylation sites with sequence features by a log‐odds ratio approachProteins-Structure Function and Bioinformatics, 2007
- Alternative splicing in cancer: Noise, functional, or systematic?The International Journal of Biochemistry & Cell Biology, 2007
- Role of intrinsic disorder in transient interactions of hub proteinsProteins-Structure Function and Bioinformatics, 2007
- Assessing protein disorder and induced foldingProteins-Structure Function and Bioinformatics, 2005
- Exploiting heterogeneous sequence properties improves prediction of protein disorderProteins-Structure Function and Bioinformatics, 2005
- Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signalingJournal of Molecular Recognition, 2005
- Predicting intrinsic disorder from amino acid sequenceProteins-Structure Function and Bioinformatics, 2003
- NACP, A Protein Implicated in Alzheimer's Disease and Learning, Is Natively UnfoldedBiochemistry, 1996