DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression (Science, 2008, 319:202-206)

報告日期: 2008/05/20
報告時間: 15:10/16:00
報告學生: 施惠瀅(英文報告)
講評老師: 洪建中



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

Science. 2008 Jan 11;319,202-6


Commentator : Jan-Jong Hung

Speaker : Hui-Ying Shih

Date  : 5/20/2008

Room : 602




Efficient in vivo transcription is accompanied by N-terminal modifications of histones. And after estrogen activation, ER a interacts with transcription factor that covalently modifies histone protein with nucleosome and control gene expression. But so far it is not clear about the dynamic change in the epigenetic- affected gene expression. The author examined the molecular mechanism by which specific methylation and demethylation of lysines in histone H3 governs hormone-induced transcription. They used the 3C (Chromosome conformation capture) technique (1) and found the chromosome form a loop when estrogen binds the ERE, and recruits cofactor to the promoter and enhancer sites.  They demonstrated estrogen receptor bound to DNA can regulate transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. In this process, lysine-specific demethylase LSD1 causes receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites. The demethylation process produces hydrogen peroxide and modifies the surrounding DNA. In this process, the 8-oxoguanine-DNA glycosylase 1 (OGG1) and topoisomerase II are recruited, whereby chromatin and DNA undergo conformational changes that are essential for estrogen-induced gene transcription.




1.   Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science (New York, NY 2002;295(5558):1306-11.