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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 05, 2013 |
| Title |
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β and coregulators [expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The closely related transcription factors (TFs), estrogen receptors ERα and ERβ, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing MCF-7 breast cancer cells with ERα, ERβ, or both receptors as a model system to define the basis of differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin-binding and transcription-regulating modules.
Cistrome and transcriptome analyses and use of clustering algorithms delineated 11 clusters representing different chromatin-bound receptor and coregulator assemblies that could be functionally associated through enrichment analysis with distinct patterns of gene regulation and preferential coregulator usage, RIP140 with ERβ and SRC3 with ERα. The receptors modified each other’s transcriptional effect, and ERβ countered the proliferative drive of ERα through several novel mechanisms associated with specific binding site clusters. Our findings delineate distinct TF-coregulator assemblies that function as control nodes specifying precise patterns of gene regulation, proliferation, and metabolism, as exemplified by two of the most important nuclear hormone receptors in human breast cancer.
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| Overall design |
MCF-7 cells expressing endogenous ERalpha were infected with adenovirus carrying either estrogen receptor beta (AdERb) or no insert (Ad) at multiplicity of infection (moi) of 50. ERβ only cells were generated from these cells by knockdown of ERα in parental cells using the following siERα sequences from Dharmacon: forward, 5’-UCAUCGCAUUCCUUGCAAAdTdT-3’, and reverse, 5’-UUUGCAAGGAAUGCGAUGAdTdT-3’. siRNA experiments were performed as previously described, and resulted in knocknown of ERα mRNA and protein by greater than 95% (GSE4006, PMID 16809442). Briefly, cells were transfected with 20 nM siCtrl [GSE4006] or siERα for 48 h after infection. Then cells were treated with 0.1% EtOH (Veh) or 10 nM E2 (Sigma-Aldrich) for 24h. All experiments were conducted with two replicates.
key words; Adenovirus infection,siRNA knock-down, ligand treatment
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| Contributor(s) |
Erdogan ZM, Katzenellenbogen BS |
| Citation(s) |
23774759 |
| Submission date |
Nov 16, 2012 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Zeynep Madak Erdogan |
| Organization name |
UIUC
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| Department |
FSHN
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| Lab |
Zeynep Madak Erdogan
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| Street address |
1201 S Goodwin Ave
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| City |
Urbana |
| State/province |
IL |
| ZIP/Postal code |
61801 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE42349 |
Integrative genomics of gene regulation by estrogen receptors and and coregulators |
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| Relations |
| BioProject |
PRJNA181135 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42347_RAW.tar |
7.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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