Estrogens, upon recruitment of their cognate receptors, govern the expression of target genes. Perillo et al. show that transcription of estrogen-responsive genes is driven by hormone-dependent demethylation of a critical lysine in histone H3 to induce a local oxidative burst that modifies the surrounding DNA by guanine oxidation, which is subsequently removed by specific glycosylases. 8-oxo-guanine-DNA glycosylase 1 and the topoisomerase IIβ enzyme are recruited to these loci and bend the intervening DNA-chromatin region to mark the site where transcription begins and drive expression of estrogen-responsive genes.
B. Perillo, M. N. Ombra, A. Bertoni, C. Cuozzo, S. Sacchetti, A. Sasso, L. Chiariotti, A. Malorni, C. Abbondanza, E. V. Avvedimento, DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression. Science 319, 202-206 (2008). [Abstract] [Full Text]