Whole-Genome Cartography of Estrogen Receptor a Binding Sites
Whole-Genome Cartography of Estrogen Receptor a Binding Sites Chin-Yo Lin1[¤, Vinsensius B. Vega1[, Jane S. Thomsen1, Tao Zhang1, Say Li Kong1, Min Xie1, Kuo Ping Chiu1, Leonard Lipovich1, Daniel H. Barnett2, Fabio Stossi2, Ailing Yeo3, Joshy George1, Vladimir A. Kuznetsov1, Yew Kok Lee1, Tze Howe Charn1, Nallasivam Palanisamy1, Lance D. Miller1, Edwin Cheung1,3, Benita S. Katzenellenbogen2, Yijun Ruan1, Guillaume Bourque1, Chia-Lin Wei1, Edison T. Liu1* 1 Genome Institute of Singapore, Singapore, Republic of Singapore, 2 Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America, 3 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor a (ERa) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERa binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (.5 kb from 59 and 39 ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERa binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERa-positive from ERa-negative breast tumors.
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