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

被引：431

作者：

Perillo, Bruno ^{[1
]}

Ombra, Maria Neve ^{[1
]}

Bertoni, Alessandra ^{[2
]}

Cuozzo, Concetta ^{[3
]}

Sacchetti, Silvana ^{[3
]}

Sasso, Annarita ^{[2
]}

Chiariotti, Lorenzo ^{[2
]}

Malorni, Antonio ^{[1
]}

Abbondanza, Ciro ^{[4
]}

Avvedimento, Enrico V. ^{[2
]}

机构：

[1] CNR, Ist Sci Alimentaz, I-83100 Avellino, Italy

[2] Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol L Calif, I-80131 Naples, Italy

[3] Ctr Ingn Genet CEINGE, Naples Oncogenom Ctr, I-80131 Naples, Italy

[4] Univ Naples 2, Dipartimento Patol Gen, I-80138 Naples, Italy

来源：

SCIENCE | 2008年 / 319卷 / 5860期

关键词：

D O I：

10.1126/science.1147674

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 II beta, 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.

引用

页码：202 / 206

页数：5

共 25 条

[11] THE NUCLEAR RECEPTOR SUPERFAMILY - THE 2ND DECADE [J].