Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Tissue-type specific estrogen signaling in breast and uterine cancer cells

ABSTRACT: Estrogen receptors play critical roles in both the normal physiological, and disease states of numerous tissues, including breast and uterus. Estrogen receptor alpha (ER) can activate or repress the expression of target genes upon estrogen stimulation. In order to better understand the transcriptional network of ER in breast and uterus, we generated genome wide maps ofM-BM- ER binding sites (ERBS) and gene expression profiles in breast cancer cells (MCF7 and T47D) and uterine cancer cells (ECC1 and Ishikawa) through ChIP-Seq and microarray techniques. Surprisingly, we identified large scale differences in the numbers of ERBS between these cell lines when treated with E2 (17-M-NM-2 estradiol). Besides identification of common and unique ERBS between breast and uterine cancer cell types., our data also suggest that both cell types could recruit a large set of common co-operating transcription factors (Co-TFs) and a few unique Co-TFs as well. Besides the genes that are commonly regulatedM-BM- between the different cell lines, there are a number of genes that are differentially regulated in different cell types. Gene pathway analyses of E2 target genes suggest that ER regulates many biological pathways and processes in both tissue-type dependent and independent manners. Our results showed that cell lines derived from same tissue display a greater similarity for both profiles of ERBS and gene expression, and that the differential profiles of ER and preferential recruitment of some Co-TFs are the main determinants for the differential regulation of E2 signaling in breast and uterine cancer cells. In order to explore common and distinctive features of ERM-NM-1 (estrogen receptor alpha) binding profiles between breast and uterus, we generated eight ChIP-Seq libraries for the four cell lines (MCF7, T47D, ECC1 and Ishikawa) under two different treatments (E2, ethanol). In addition, we generated four control libraries for the four cell lines. For all treatment libraries, we generated about 7-12 million unique tags each. ER antibody catalog number is (Santa Cruz,sc-543).

ORGANISM(S): Homo sapiens

SUBMITTER: Cheng Wei Chang

PROVIDER: E-GEOD-23893 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Integrative model of genomic factors for determining binding site selection by estrogen receptor-α.

Joseph Roy R Orlov Yuriy L YL Huss Mikael M Sun Wenjie W Kong Say Li SL Ukil Leena L Pan You Fu YF Li Guoliang G Lim Michael M Thomsen Jane S JS Ruan Yijun Y Clarke Neil D ND Prabhakar Shyam S Cheung Edwin E Liu Edison T ET

Molecular systems biology 20101201

A major question in transcription factor (TF) biology is why a TF binds to only a small fraction of motif eligible binding sites in the genome. Using the estrogen receptor-α as a model system, we sought to explicitly define parameters that determine TF-binding site selection. By examining 12 genetic and epigenetic parameters, we find that an energetically favorable estrogen response element (ERE) motif sequence, co-occupancy by the TF FOXA1, the presence of the H3K4me1 mark and an open chromatin ...[more]

PMID: 21179027

Publication: 1/2

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Project description:Using the estrogen receptor alpha (ERalpha) as a model ligand inducible transcription factor, we sought to explicitly define parameters that determine transcription factor binding site selection on a genomic scale in an inducible system that minimizes confounding chromatin effects by the transcription factor itself. By examining several genetic and epigenetic parameters, we find that an energetically favorable estrogen response element (ERE) motif sequence, evidence of occupancy of a "pioneering" transcription factor FOXA1, the presence of the enhancer mark, H3K4me1, and an open chromatin configuration (FAIRE) at the pre-ligand state provide specificity for ER binding. Genome-wide ChIP-sequencing was done in MCF-7 cancer cell line for the following histone H3 modifications: monomethylation H3K4me1, trimethylation H3K4me3, H3K9me3, H3K27me3, acetylation H3K9ac, H3K14ac. In addition sequencing of RNA Pol II was done at same treatment conditions (E2 and DMSO). In addition, we assessed the chromatin configuration of ERα binding sites by deeply sequencing fragments isolated by Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) (Giresi et al, 2007) which enriches for nucleosome free genomic DNA in the aqueous phase of a phenol extraction. The analysis histone modifications in MCF-7 cancer cells was done by ChIP-seq data obtained either with E2 stimulation or without stimulation using vehicle as a control. Using the ERα binding sites defined by ChIP-seq (separate submission), we analyzed the population characteristics of the chromatin configuration of the ERα binding sites. To this end, we performed ChIP-seq analysis for the occupancy configuration of each of the following marks before and after E2 exposure: RNA Pol II, the activation marks H3K4me1, H3K4me3, H3K9ac and H3K14ac, and the repression marks H3K9me3 and H3K27me3. We assessed the chromatin configuration of ERα binding sites by deeply sequencing fragments isolated by Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) (Giresi et al, 2007) which enriches for nucleosome free genomic DNA in the aqueous phase of a phenol extraction. The tag count of FAIRE fragments reflects the nucleosome depletion at any given site. RNA Pol II - Cat# ab5408, Abcam; H3K9me3 - Cat# ab8898, Abcam; H3K27me3 - Cat# 07-449, Upstate Biotechnology Inc.; H3K4me1 - Cat# ab8895, Abcam; H3K4me3 - Cat# ab8580, Abcam; H3K9ac - Cat# 07-352, Upstate Biotechnology Inc.; H3K14ac - Cat# 07-353, Upstate Biotechnology Inc.

Dataset Information

Tissue-type specific estrogen signaling in breast and uterine cancer cells

Publications

Integrative model of genomic factors for determining binding site selection by estrogen receptor-α.

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