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

Bruno Perillo, Maria Neve Ombra, Alessandra Bertoni, Concetta Cuozzo, Silvana Sacchetti, Annarita Sasso, Lorenzo Chiariotti, Antonio Malorni, Ciro Abbondanza and Enrico V. Avvedimento
Science
New Series, Vol. 319, No. 5860 (Jan. 11, 2008), pp. 202-206
Stable URL: http://www.jstor.org/stable/20051978
Page Count: 5
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DNA Oxidation as Triggered by H3K9me2 Demethylation Drives Estrogen-Induced Gene Expression
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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 topoisomerase IIβ, 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.

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