Transcriptomics

Dataset Information

415

Cellular reprogramming by the conjoint action of ERalpha, FOXA1, and GATA3 to a ligand inducible growth state


ABSTRACT: 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 the transfection of all three TFs was necessary to reprogramme 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 the enhanceosome components comprising ERalpha, FOXA1 and GATA3 are necessary for the full repertoire of cancer associated effects of the ERalpha. Illumina HumanRef-8 v3 Expression BeadChip was used to measure the gene expression levels from ERalpha negative breast cancer cell MDA-MB-231 with different transfections: with vector control, with ERalpha only, or with ERalpha+FOXA1+GATA3 combined.

ORGANISM(S): Homo sapiens  

SUBMITTER: Guoliang Li   Edison T Liu  Say L Kong 

PROVIDER: E-GEOD-30574 | ArrayExpress | 2011-09-04

SECONDARY ACCESSION(S): GSE30574PRJNA143371

REPOSITORIES: GEO, ArrayExpress

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Publications

Cellular reprogramming by the conjoint action of ERα, FOXA1, and GATA3 to a ligand-inducible growth state.

Kong Say Li SL   Li Guoliang G   Loh Siang Lin SL   Sung Wing-Kin WK   Liu Edison T ET  

Molecular systems biology 20110830


Despite the role of the estrogen receptor α (ERα) pathway as a key growth driver for breast cells, the phenotypic consequence of exogenous introduction of ERα into ERα-negative cells paradoxically has been growth inhibition. We mapped the binding profiles of ERα and its interacting transcription factors (TFs), FOXA1 and GATA3 in MCF-7 breast carcinoma cells, and observed that these three TFs form a functional enhanceosome that regulates the genes driving core ERα function and cooperatively modul  ...[more]

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