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Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements
You F.P.1; Wansa K.D.S.A.1; Mei H.L.1; Zhao B.1; Shu Z.H.1; Peck Y.T.1; Kar S.L.1; Bourque G.1; Liu E.T.1; Cheung E.1
2008-11-21
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume283Issue:47Pages:32977-32988
Abstract

Nuclear signaling by estrogens rapidly induces the global recruitment of estrogen receptors (ERs) to thousands of highly specific locations in the genome. Here, we have examined whether ER binding sites that are located distal from the transcription start sites of estrogen target genes are functionally relevant. Similar to ER binding sites near the proximal promoter region, ER binding sites located at distal locations are occupied by ERs after estrogen stimulation. And, like proximal bound ERs, ERs occupied at distal sites can recruit coactivators and the RNA polymerase transcription machinery and mediate specific structural changes to chromatin. Furthermore, ERs occupied at the distal sites are capable of communicating with ERs bound at the promoter region, possibly via long range chromosome looping. In functional analysis, disruption of the response elements in the distal ER binding sites abrogated ER binding and significantly reduced transcriptional response. Finally, sequence comparison of the response elements at the distal sites suggests a high level of conservation across different species. Together, our data indicate that distal ER binding sites are bona fide transcriptional enhancers that are involved in long range chromosomal interaction, transcription complex formation, and distinct structural modifications of chromatin across large genomic spans. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI10.1074/jbc.M802024200
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000260893700086
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被引频次[WOS]:69   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Faculty of Health Sciences
Affiliation1.A-Star, Genome Institute of Singapore
2.Nanyang Technological University
3.Yong Loo Lin School of Medicine
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You F.P.,Wansa K.D.S.A.,Mei H.L.,et al. Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements[J]. Journal of Biological Chemistry,2008,283(47):32977-32988.
APA You F.P..,Wansa K.D.S.A..,Mei H.L..,Zhao B..,Shu Z.H..,...&Cheung E..(2008).Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements.Journal of Biological Chemistry,283(47),32977-32988.
MLA You F.P.,et al."Regulation of estrogen receptor-mediated long range transcription via evolutionarily conserved distal response elements".Journal of Biological Chemistry 283.47(2008):32977-32988.
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