The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation, particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer.
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The authors would like to thank D. Lynch, M. Lupien, M. Laza and O. Jänne for helpful discussions and review of the manuscript. This work was supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (DK074967) and the US National Cancer Institute–sponsored Dana-Farber/Harvard Cancer Center Breast Cancer SPORE Grant (CA089393); by the Claudia Adams Barr Program in Innovative Basic Cancer Research (M.B., P.A.S., X.S.L.); by US Department of Defense Breast Cancer Research Program Awards (M.B., J.S.C.) and by fellowships from the Fondation Recherche Medicale (J.E.), the Susan G. Komen Breast Cancer Foundation (E.K.K.) and the US National Institutes of Health (T.R.G. and C.A.M.).
T.R. Gingeras is an employee of Affymetrix, Inc.
Validation of ER binding sites adjacent to estrogen target genes. (PDF 41 kb)
Assessment of mechanisms of early and late gene repression. (PDF 100 kb)
Pairwise analysis of motifs at different cutoff scores. (PDF 61 kb)
ER binding at previously characterized putative ER binding sites. (PDF 76 kb)
Enriched motifs within ER binding sites. (PDF 42 kb)
Primer sequences. (PDF 48 kb)
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Carroll, J., Meyer, C., Song, J. et al. Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38, 1289–1297 (2006) doi:10.1038/ng1901
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