Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide analysis of ERalpha binding sites in U2OS-ERalpha cells

ABSTRACT: ChIP followed by deep sequencing was performed with antibodies to ERalpha in U2OS-ERalpha cells treated with 17beta-estradiol. Examination of Eralpha binding sites in U2OS-Eralpha cells. Sequenced input was used as a control

ORGANISM(S): Homo sapiens

SUBMITTER: susan krum

PROVIDER: E-GEOD-28918 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription.

Miranda-Carboni Gustavo A GA Guemes Miriam M Bailey Shannon S Anaya Edgar E Corselli Mirko M Peault Bruno B Krum Susan A SA

Molecular endocrinology (Baltimore, Md.) 20110512 7

Estrogens regulate osteoblast differentiation and mineralization. We identified GATA4 as a transcription factor expressed in osteoblasts and directly regulated by 17β-estradiol in this cell type but not in breast cancer cells, another estrogen-responsive tissue. Chromatin immunoprecipitation sequencing (chromatin immunoprecipitation sequencing) reveals that estrogen receptor α (ERα) binds to chromatin near GATA4 at five different enhancers. GATA4 and ERα are both recruited to ERα binding sites n ...[more]

PMID: 21566084

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Project description:We are using ACI and BN rats, which differ markedly in their susceptibility to 17beta-Estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks and cell proliferation, apoptosis, differentiation and gene expression were evaluated. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the extracellular matrix (ECM). Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in part, the differences in mammary cancer susceptibility exhibited by ACI and BN rats. Two groups of 17beta-estradiol treated female rats were compared. Five ACI and five BN rats were treated with 17beta-estradiol for 12 weeks. Total RNA was isolated from the mammary glands of these animals, labeled, and hybridized to Affymetrix Rat Genome 230 2.0 Arrays (Affymetrix Inc.). Significantly differentially expressed genes were found between these groups.

Dataset Information

Genome-wide analysis of ERalpha binding sites in U2OS-ERalpha cells

Publications

GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription.

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