PMID:18187655
| Citation |
Perillo, B, Ombra, MN, Bertoni, A, Cuozzo, C, Sacchetti, S, Sasso, A, Chiariotti, L, Malorni, A, Abbondanza, C and Avvedimento, EV (2008) DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression. Science 319:202-6 |
|---|---|
| Abstract |
Modifications at the N-terminal tails of nucleosomal histones are required for efficient transcription in vivo. We analyzed how H3 histone methylation and demethylation control expression of estrogen-responsive genes and show that a DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. This process is driven by receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites and is achieved by activation of resident LSD1 demethylase. Localized demethylation produces hydrogen peroxide, which modifies the surrounding DNA and recruits 8-oxoguanine-DNA glycosylase 1 and topoisomeraseIIbeta, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription. Our data show a strategy that uses controlled DNA damage and repair to guide productive transcription. |
| Links |
PubMed Online version:10.1126/science.1147674 |
| Keywords |
Cell Line, Tumor; Cells, Cultured; Chromatin/metabolism; DNA/metabolism; DNA Damage; DNA Glycosylases/metabolism; DNA Repair; DNA Topoisomerases, Type II/metabolism; DNA-Binding Proteins/metabolism; Enhancer Elements, Genetic; Estradiol/metabolism; Estrogen Receptor alpha/metabolism; Gene Expression Regulation; Genes, bcl-2; Guanine/analogs & derivatives; Guanine/metabolism; Histone Demethylases; Histones/metabolism; Humans; Hydrogen Peroxide/metabolism; Lysine/metabolism; Methylation; Nucleic Acid Conformation; Oxidation-Reduction; Oxidoreductases, N-Demethylating/metabolism; Promoter Regions, Genetic; RNA Polymerase II/metabolism; Transcription, Genetic |
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