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Title: Chromatin immunoprecipitation profiling of human breast cancer cell lines and tissues to identify novel estrogen receptor-{alpha} binding sites and estradiol target genes      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
03-27-2012
ID:
E-GEOD-11506
description:
Estrogen receptor-{alpha} (ER{alpha}) and its ligand estradiol play critical roles in breast cancer growth and are important therapeutic targets for this disease. Using chromatin immunoprecipitation (ChIP)-on-chip, ligand-bound ER{alpha} was recently found to function as a master transcriptional regulator via binding to many cis-acting sites genome-wide. Here, we used an alternative technology (ChIP cloning) and identified 94 ER{alpha} target loci in breast cancer cells. The ER{alpha}-binding sites contained both classic estrogen response elements and nonclassic binding sequences, showed specific transcriptional activity in reporter gene assay, and interacted with the key transcriptional regulators, including RNA polymerase II and nuclear receptor coactivator-3. The great majority of the binding sites were located in either introns or far distant to coding regions of genes. Forty-three percent of the genes that lie within 50 kb to an ER{alpha}-binding site were regulated by estradiol. Most of these genes are novel estradiol targets encoding receptors, signaling messengers, and ion binders/transporters. mRNA profiling in estradiol-treated breast cancer cell lines and tissues revealed that these genes are highly ER{alpha} responsive both in vitro and in vivo. Among estradiol-induced genes, Wnt11 was found to increase cell survival by significantly reducing apoptosis in breast cancer cells. Taken together, we showed novel genomic binding sites of ER{alpha} that regulate a novel set of genes in response to estradiol in breast cancer. Our findings suggest that at least a subset of these genes, including Wnt11, may play important in vivo and in vitro biological roles in breast cancer. Experiment Overall Design: This Series currently contains the gene expression data accompanying Zhihong Lin et al. Cancer Research 67,5017-5024(2007). MCF7 cells were treated with vehicle or E2 at a concentration of 10E-9 mol/L for 3 and 6 h. All experiments were performed in triplicate.
keywords:
ChIP-chip by array
format:
HTML
storedIn:
Array Express
qualifier:
not compressed
accessType:
landing page
authorization:
none
authentication:
none
primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-11506
format:
JSON
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-11506.json
format:
XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-11506.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/