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DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression
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DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression
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Journal Article
DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression
2008
Overview
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 topoisomeraseIIβ, 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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ DNA
/ DNA Glycosylases - metabolism
/ DNA Topoisomerases, Type II - metabolism
/ DNA-Binding Proteins - metabolism
/ Enzymes
/ Estrogen Receptor alpha - metabolism
/ Genes
/ Genetics
/ Guanine - analogs & derivatives
/ Histones
/ Humans
/ Hydrogen Peroxide - metabolism
/ lysine
/ Oxidoreductases, N-Demethylating - metabolism
/ RNA
