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

Modifications at the N-terminal tails of nucleosomal histones a re re quired for effici ent transcription in vivo. W e a nalyzed how H3 histone methylation and demethylation cont rol e xpression of estrog en-responsive g enes and s how t hat a DNA-bound e strog en r ecep tor directs transcription b y p articipa t ing i n be n ding chromati n t o contact the RNA polyme rase II re crui ted t o t he p r omote r. This process i s driven by r eceptor-targeted demethyl atio n o f H 3 l ysine 9 at both enhancer and p romoter sites and is achieved by activation of re sident LSD1 demethylase. Localized d emethylation produces hydrogen peroxide, which modifies the s urrounding DNA and recruits 8-oxog uanine–DNA glycosylase 1and topoisomeraseIIb, t riggering chromatin and DNA c onfo rmational c hanges that are e ssential for e st rogen-induced t ranscr iption. O ur data show a s trategy t hat uses c ontrolled D NA damage and repair to guide prod uctive tra n scription.