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| Status |
Public on Dec 11, 2022 |
| Title |
Analysis of the impact of FOXA1 expression on MDA::ER E2-sensitive transcriptomes and ER cistromes [Transcriptome data] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The primordial actions of the estrogen receptor alpha (ER) in controlling breast cancer cells proliferation rate are particularly documented. However, reintroducing ER into ER-negative cells does not reprogram their transcriptome towards an estrogen-sensitive growth phenotype. Member of the Forkhead (FKH) family of transcription factors, FOXA1 has been characterized to be essential for the appropriate binding of ER onto chromatin in MCF-7 cells. FOXA1 pioneering actions involve modulations of histone post-translational modifications (HPTMs) and local depletion in methylated CpGs. Using MDA-MB231 cells which are ER and FOXA1 negative, we aimed at determining whether the introduction of ER and FOXA1 would be sufficient to restore an estrogen-sensitive growth and to coincidently reprogram chromatin. We used ChIP-seq experiments to map ER and FOXA1 binding sites (BSs) and to profile H3K4me2 and H3K27ac marks, and surprisingly observed that FOXA1 had rather a global negative impact on ER actions, associated with an inhibition of growth and a reorientation of the transcriptome of the cells towards cell death. We demonstrate that the re-introduction of FOXA1 in these cells actually competes for the binding and pioneering actions of FOXA2, another FKH protein, on a number of ER BSs. As demonstrated for its alter ego FOXA1 in MCF-7 cells, abrogating FOXA2 expression drastically diminished ER binding onto its cognate sites, associated with a local loss of HPTMs for active chromatin.
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| Overall design |
A 12 chip study aiming to characterize Estradiol (E2)-sensitive genes in MDA::ER cells conditionnally expressing FOXA1 following a 4h treatment with E2. RNAs were prepared from three independent triplicate experiments. Each of the three technical replicate correspond to pooled RNAs from 1 experiment. Controls for these experiments are 6 arrays corresponding to vehicle-treated cells.
This submission represents transcriptome component of study.
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| Contributor(s) |
Quintin J, Le Péron C, Mahé E, Sérandour AA, Palierne G, Bizot M, Percevault F, Avner S, Salbert G, Métivier R |
| Citation missing |
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| |
| Submission date |
Mar 07, 2014 |
| Last update date |
Dec 12, 2022 |
| Contact name |
Raphaël Métivier |
| E-mail(s) |
raphael.metivier@univ-rennes1.fr
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| Organization name |
CNRS UMR 6290
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| Lab |
SP@RTE
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| Street address |
Campus de Beaulieu
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| City |
Rennes |
| ZIP/Postal code |
35042 Cedex |
| Country |
France |
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| Platforms (1) |
| GPL15143 |
NimbleGen Human Expression Array [2006-08-03_HG18_60mer_expr] |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE55741 |
Analysis of the impact of FOXA1 expression on MDA::ER E2-sensitive transcriptomes and ER cistromes |
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| Relations |
| BioProject |
PRJNA240535 |
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