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Molecular Endocrinology, doi:10.1210/me.2007-0121
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*ESTRADIOL
Molecular Endocrinology 22 (1): 10-22
Copyright © 2008 by The Endocrine Society

Genome-Wide Identification of Estrogen Receptor {alpha}-Binding Sites in Mouse Liver

Hui Gao, Susann Fält, Albin Sandelin, Jan-Åke Gustafsson and Karin Dahlman-Wright

Department of Biosciences and Nutrition (H.G., S.F., J.-A.G., K.D.-W.), Karolinska Institutet, Novum, S141 57 Huddinge, Sweden; and The Bioinformatics Centre (A.S.), Department of Molecular Biology & Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 København N, Denmark

Address all correspondence and requests for reprints to: Hui Gao, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden. E-mail: hui.gao{at}biosci.ki.se.

We report the genome-wide identification of estrogen receptor {alpha} (ER{alpha})-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ER{alpha}-binding regions. In agreement with what has previously been reported for human cell lines, many ER{alpha}-binding regions are located far away from transcription start sites; approximately 40% of ER{alpha}-binding regions are located within 10 kb of annotated transcription start sites. Almost 50% of ER{alpha}-binding regions overlap genes. The majority of ER{alpha}-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS proteins, and Forkhead proteins as the most common motifs present in identified ER{alpha}-binding regions. To correlate ER{alpha} binding to the promoter of specific genes, with changes in expression levels of the corresponding mRNAs, expression levels of selected mRNAs were assayed in livers 2, 4, and 6 h after treatment with ER{alpha}-selective agonist propyl pyrazole triol. Five of these eight selected genes, Shp, Stat3, Pdgds, Pck1, and Pdk4, all responded to propyl pyrazole triol after 4 h treatment. These results extend our previous studies using gene expression profiling to characterize estrogen signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ER{alpha} to DNA in intact chromatin.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα
Ligands:   17β-Estradiol



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