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| Status |
Public on Jun 30, 2010 |
| Title |
Genome-Wide Analysis of Estrogen Receptor-α DNA Binding and Tethering Mechanisms |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| |
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| Overall design |
Refer to individual Series
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| |
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| Citation(s) |
20547749 |
| Submission date |
Jun 29, 2010 |
| Last update date |
Feb 21, 2019 |
| Contact name |
Joshua D Stender |
| Organization name |
University of California at San Diego
|
| Street address |
9500 Gillman
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (26)
|
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| This SuperSeries is composed of the following SubSeries: |
| GSE22593 |
WT and DBDmut Breast Cancer Cells |
| GSE22609 |
Genome-Wide Maps of WT and DBDmut Estrogen Receptor in Human Breast Cancer Cells |
|
| Relations |
| BioProject |
PRJNA128349 |
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