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Series GSE29073 Query DataSets for GSE29073
Status Public on Sep 05, 2011
Title Cellular reprogramming by the conjoint action of ERalpha, FOXA1 and GATA3 to a ligand-inducible growth state
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Despite the role of the estrogen receptor alpha (ERalpha) pathway as a key growth driver for breast cells, the phenotypic consequence of exogenous introduction of ERalpha into ERalpha-negative cells paradoxically has been growth inhibition. We map the binding profiles of ERalpha and its interacting transcription factors (TFs), FOXA1 and GATA3, in MCF-7 breast carcinoma cells. We observe that these three TFs form a functional enhanceosome and cooperatively modulate the transcriptional networks previously ascribed to ERalpha alone. We demonstrate that these enhanceosome-occupied sites are associated with optimal enhancer characteristics with highest p300 coactivator recruitment, RNA Pol II occupancy, and chromatin opening. The enhancesome binding sites appear to regulate the genes driving core ERalpha function. Most importantly, we show that transfection of all three TFs was necessary to reprogram the ERalpha-negative MDA-MB-231 and BT-459 cells to restore the estrogen responsive growth and to transcriptionally resemble the estrogen-treated ERalpha-positive MCF-7 cells. Cumulatively, these results suggest that all of the enhanceosome components comprising ERalpha, FOXA1 and GATA3 are necessary for the full repertoire of the cancer-associated effects of the ERalpha.
Overall design The analysis of ERalpha, FOXA1, and GATA3 in MCF-7 cancer cells was done by ChIP-seq data obtained either with estradiol (E2) stimulation or without stimulation using vehicle as a control. Using the ERalpha bindings defined by ChIP-seq (GSE23893), FOXA1 bindings (GSE26831), and GATA3 bindings (this Series), we analyzed the enhanceosome effect of the overlapped binding sites from ERalpha, FOXA1 and GATA3.
Contributor(s) Kong SL, Li G, Liu ET
Citation(s) 21878914
Submission date May 04, 2011
Last update date May 15, 2019
Contact name Guoliang Li
Organization name Genome Institute of Singapore
Department Computational and Systems Biology
Street address 60 Biopolis Street, #02-01, Genome
City Singapore
ZIP/Postal code 138672
Country Singapore
Platforms (1)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
Samples (4)
GSM720422 GATA3 sequencing in estradiol (E2) treated MCF-7 cells
GSM720423 GATA3 sequencing in non-treated (DMSO as vehicle) MCF-7 cells
GSM720424 p300 sequencing in estradiol (E2) treated MCF-7 cells
SRA SRP006701
BioProject PRJNA140285

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Supplementary file Size Download File type/resource
GSE29073_RAW.tar 769.8 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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