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.

DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression / Perillo, B; Ombra, Mn; Bertoni, A; Cuozzo, C; Sacchetti, S; Sasso, A; Chiariotti, Lorenzo; Malorni, A; Abbondanza, C; Avvedimento, VITTORIO ENRICO. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 319:5860(2008), pp. 202-206.

DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression.

CHIARIOTTI, LORENZO;AVVEDIMENTO, VITTORIO ENRICO
2008

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.
2008
DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression / Perillo, B; Ombra, Mn; Bertoni, A; Cuozzo, C; Sacchetti, S; Sasso, A; Chiariotti, Lorenzo; Malorni, A; Abbondanza, C; Avvedimento, VITTORIO ENRICO. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 319:5860(2008), pp. 202-206.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/343223
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