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Series GSE42347 Query DataSets for GSE42347
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
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.
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
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
Department FSHN
Lab Zeynep Madak Erdogan
Street address 1201 S Goodwin Ave
City Urbana
State/province IL
ZIP/Postal code 61801
Country USA
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (4)
GSM1038218 AdERbetasiERalphaVeh rep1
GSM1038219 AdERbetasiERalphaVeh rep2
GSM1038220 AdERbetasiERalphaE2 rep1
This SubSeries is part of SuperSeries:
GSE42349 Integrative genomics of gene regulation by estrogen receptors and and coregulators
BioProject PRJNA181135

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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