Genome-Wide Identification of High-Affinity Estrogen Response Elements in Human and Mouse (original) (raw)
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1Département de Biochimie (V.B., J.D., D.N., S.M.), Université de Montréal, Montréal, Québec, Canada H3C 3J7
2Departments of Physiology (V.B., J.H.W.), Québec, Canada H3G 1Y6
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1Département de Biochimie (V.B., J.D., D.N., S.M.), Université de Montréal, Montréal, Québec, Canada H3C 3J7
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5European Molecular Biology Laboratories (R.M., N.B., F.G.), D-69117 Heidelberg, Germany
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4McGill University and Genome Québec Innovation Centre (Y.N.), Montréal, Québec, Canada H3A 1A4
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1Département de Biochimie (V.B., J.D., D.N., S.M.), Université de Montréal, Montréal, Québec, Canada H3C 3J7
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5European Molecular Biology Laboratories (R.M., N.B., F.G.), D-69117 Heidelberg, Germany
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5European Molecular Biology Laboratories (R.M., N.B., F.G.), D-69117 Heidelberg, Germany
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2Departments of Physiology (V.B., J.H.W.), Québec, Canada H3G 1Y6
3Medicine (J.H.W., S.M.), McGill University, Montréal, Québec, Canada H3G 1Y6
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1Département de Biochimie (V.B., J.D., D.N., S.M.), Université de Montréal, Montréal, Québec, Canada H3C 3J7
3Medicine (J.H.W., S.M.), McGill University, Montréal, Québec, Canada H3G 1Y6
*Address all correspondence and requests for reprints to: Sylvie Mader, Département de Biochimie, Université de Montréal, CP 6128 Succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7.
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Received:
13 November 2003
Accepted:
26 February 2004
Cite
Véronique Bourdeau, Julie Deschênes, Raphaël Métivier, Yoshihiko Nagai, Denis Nguyen, Nancy Bretschneider, Frank Gannon, John H. White, Sylvie Mader, Genome-Wide Identification of High-Affinity Estrogen Response Elements in Human and Mouse, Molecular Endocrinology, Volume 18, Issue 6, 1 June 2004, Pages 1411–1427, https://doi.org/10.1210/me.2003-0441
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Abstract
Although estrogen receptors (ERs) recognize 15-bp palindromic estrogen response elements (EREs) with maximal affinity in vitro, few near-consensus sequences have been characterized in estrogen target genes. Here we report the design of a genome-wide screen for high-affinity EREs and the identification of approximately 70,000 motifs in the human and mouse genomes. EREs are enriched in regions proximal to the transcriptional start sites, and approximately 1% of elements appear conserved in the flanking regions (−10 kb to +5 kb) of orthologous human and mouse genes. Conserved and nonconserved elements were also found, often in multiple occurrences, in more than 230 estrogen-stimulated human genes previously identified from expression studies. In genes containing known EREs, we also identified additional distal elements, sometimes with higher in vitro binding affinity and/or better conservation between the species considered. Chromatin immunoprecipitation experiments in breast cancer cell lines indicate that most novel elements present in responsive genes bind ERα in vivo, including some EREs located up to approximately 10 kb from transcriptional start sites. Our results demonstrate that near-consensus EREs occur frequently in both genomes and that whereas chromatin structure likely modulates access to binding sites, far upstream elements can be evolutionarily conserved and bind ERs in vivo.
Copyright © 2004 by The Endocrine Society
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