Genome-Wide Maps of WT and DBDmut Estrogen Receptor in Human Breast Cancer Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22609 | GEO | 2010/06/30
SECONDARY ACCESSION(S): PRJNA129093
REPOSITORIES: GEO
Similar Datasets
Project description:We wanted to explore the relative contributions of DNA binding and tethering regulation modes by the estrogen receptor in human breast cancer cells We defined the genome-wide localization of WT and DBDmut estrogen receptors in human breast cancer cells
2010-06-30 | E-GEOD-22609 | biostudies-arrayexpress
Project description:The nuclear receptor, estrogen receptor alpha (ERα), controls the expression of hundreds of genes responsible for target cell phenotypic properties, but the relative importance of direct vs. tethering mechanisms of DNA binding has not been established. In this first report, we examine the genome-wide chromatin localization of an altered-specificity mutant ER with a DNA-binding domain deficient in binding to estrogen response element (ERE)-containing DNA (DBDmut ER) vs. wild type ERα. Using high-throughput sequencing of ER chromatin immunoprecipitations (ChIP-Seq) and mRNA transcriptional profiling, we show that direct ERE binding is required for most (75%) estrogen-dependent gene regulation and 90% of hormone-dependent recruitment of ER to genomic binding sites. De novo motif analysis of the chromatin binding regions in MDA-MB-231 human breast cancer cells defined unique transcription factor profiles responsible for genes regulated through tethering vs. direct DNA (ERE) binding, with Runx motifs enriched in ER-tethered sites. We confirmed a role for Runx1 in mediating ERa genomic recruitment and regulation of tethering genes. Our findings delineate the contributions of ERE binding vs. binding through response elements for other transcription factors in chromatin localization and ER-dependent gene regulation, paradigms likely to underlie the gene regulatory actions of other nuclear receptors as well. This SuperSeries is composed of the following subset Series: GSE22593: WT and DBDmut Breast Cancer Cells GSE22609: Genome-Wide Maps of WT and DBDmut Estrogen Receptor in Human Breast Cancer Cells Refer to individual Series
2010-06-29 | E-GEOD-22610 | biostudies-arrayexpress
Project description:The nuclear receptor, estrogen receptor alpha (ERα), controls the expression of hundreds of genes responsible for target cell phenotypic properties, but the relative importance of direct vs. tethering mechanisms of DNA binding has not been established. In this first report, we examine the genome-wide chromatin localization of an altered-specificity mutant ER with a DNA-binding domain deficient in binding to estrogen response element (ERE)-containing DNA (DBDmut ER) vs. wild type ERα. Using high-throughput sequencing of ER chromatin immunoprecipitations (ChIP-Seq) and mRNA transcriptional profiling, we show that direct ERE binding is required for most (75%) estrogen-dependent gene regulation and 90% of hormone-dependent recruitment of ER to genomic binding sites. De novo motif analysis of the chromatin binding regions in MDA-MB-231 human breast cancer cells defined unique transcription factor profiles responsible for genes regulated through tethering vs. direct DNA (ERE) binding, with Runx motifs enriched in ER-tethered sites. We confirmed a role for Runx1 in mediating ERa genomic recruitment and regulation of tethering genes. Our findings delineate the contributions of ERE binding vs. binding through response elements for other transcription factors in chromatin localization and ER-dependent gene regulation, paradigms likely to underlie the gene regulatory actions of other nuclear receptors as well. This SuperSeries is composed of the SubSeries listed below.
2010-06-30 | GSE22610 | GEO
Project description:Estrogen protects females from hepatocellular carcinoma (HCC). To determine whether this protection is mediated by classic estrogen receptors, we tested HCC susceptibility in estrogen receptor-deficient mice. In contrast to a previous study, we found that diethylnitrosamine induces hepatocarcinogenesis to a much greater extent when females lack Esr1, which encodes Estrogen Receptor-α. Relative to wild-type littermates, Esr1 knockout females developed 9-fold more tumors. Deficiency of Esr2, which encodes Estrogen Receptor-β, did not affect liver carcinogenesis in females. Using microarrays and QPCR to examine estrogen receptor effects on hepatic gene expression patterns, we found that germline Esr1 deficiency resulted in the masculinization of gene expression in the female liver.
2021-02-28 | GSE164900 | GEO
Project description:The Estrogen Receptor alpha (ERα) controls key cellular functions in hormone responsive breast cancer by assembling in large functional multiprotein complexes. ERα ligands are classified as agonists and antagonist, according to the response they elicit, thus the molecular characterization of the of ERα nuclear iteractome composition following estrogen and antiestrogen stimulation whose is needed to understand their effects on estrogen target tissues, in particular breast cancer. To this aim interaction proteomics coupled to mass spectrometry (MS) was applied to map the ERα nuclear interacting partners in MCF7 breast cancer cell nuclei following estrogen and antiestrogen stimuli.
2020-09-02 | PXD018709 | Pride
Project description:Comparison between Estrogen receptor positive and Estrogen receptor negative breast cancer samples Keywords: breast cancer type comparison
2008-09-17 | GSE10510 | GEO
Project description:TLE1 mediates estrogen receptor binding
| PRJEB653 | ENA
Project description:Three antibodies targeting estrogen receptor beta were evaluated with respect to their specificity towards the target protein, by immunoprecipitation followed by LC-Orbitrap MS.
2017-06-16 | PXD005936 | Pride
Project description:The human genome encodes an order of magnitude more gene expression enhancers than promoters, suggesting that most genes are regulated by the combined action of multiple enhancers. We have previously shown that neighboring estrogen-responsive enhancers, which are approximately 5,000 basepairs apart, exhibit complex synergistic contributions to the production of an estrogenic transcriptional response. Here we sought to determine the molecular underpinnings of the observed enhancer cooperativity. We generated genetic deletions of individual estrogen receptor (ER) bound enhancers and found that enhancers containing full estrogen response element (ERE) motifs control ER binding at neighboring sites, while enhancers with pre-existing histone acetylation/accessibility confer a permissible chromatin environment to the neighboring enhancers. Genome engineering revealed that a cluster of two enhancers with half EREs could not compensate for the lack of a full ERE site within the cluster. In contrast, two enhancers with full EREs produced a transcriptional response greater than the wild-type locus. By swapping genomic sequences between enhancers, we found that the genomic location in which a full ERE resides strongly influences enhancer activity. Our results lead to a model in which a full ERE is required for ER recruitment, but the presence of pre-existing histone acetylation within an enhancer cluster is also needed in order for estrogen-driven gene regulation to occur.
2020-03-18 | GSE147141 | GEO
Project description:The human genome encodes an order of magnitude more gene expression enhancers than promoters, suggesting that most genes are regulated by the combined action of multiple enhancers. We have previously shown that neighboring estrogen-responsive enhancers, which are approximately 5,000 basepairs apart, exhibit complex synergistic contributions to the production of an estrogenic transcriptional response. Here we sought to determine the molecular underpinnings of the observed enhancer cooperativity. We generated genetic deletions of individual estrogen receptor (ER) bound enhancers and found that enhancers containing full estrogen response element (ERE) motifs control ER binding at neighboring sites, while enhancers with pre-existing histone acetylation/accessibility confer a permissible chromatin environment to the neighboring enhancers. Genome engineering revealed that a cluster of two enhancers with half EREs could not compensate for the lack of a full ERE site within the cluster. In contrast, two enhancers with full EREs produced a transcriptional response greater than the wild-type locus. By swapping genomic sequences between enhancers, we found that the genomic location in which a full ERE resides strongly influences enhancer activity. Our results lead to a model in which a full ERE is required for ER recruitment, but the presence of pre-existing histone acetylation within an enhancer cluster is also needed in order for estrogen-driven gene regulation to occur.
2020-03-18 | GSE147140 | GEO