DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression

作者：Bruno Perillo, Maria Neve Ombra, Alessandra Bertoni, Concetta Cuozzo, Silvana Sacchetti, Annarita Sasso, Lorenzo Chiariotti, Antonio Malorni, Ciro Abbondanza, Enrico Vittorio Avvedimento · 发表于：Science · 年份：2008 · DOI：10.1126/science.1147674 · 被引用次数：537 · 研究领域：Epigenetics and DNA Methylation、Genomics and Chromatin Dynamics、DNA Repair Mechanisms

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.