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| Status |
Public on Oct 11, 2011 |
| Title |
Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics [mRNA profiling] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Retinoic acid (RA) triggers physiological processes by activating heterodimeric transcription factors comprising retinoic acid (RARa,b,g) and retinoid X (RXRa,b,g) receptors. How a single signal induces highly complex temporally controlled networks that ultimately orchestrate physiological processes is unclear. Using an RA-inducible differentiation model we defined the temporal changes in the genome-wide binding patterns of RARg and RXRa and correlated them with transcription regulation. Unexpectedly, both receptors displayed a highly dynamic binding, with different RXRa heterodimers targeting identical loci. Comparison of RARg and RXRa co-binding at RA-regulated genes identified putative RXRa-RARg target genes that were validated with subtype-selective agonists. Gene regulatory decisions during differentiation were inferred from transcription factor target gene information and temporal gene expression. This analysis revealed 6 distinct co-expression paths of which RXRa-RARg is associated with transcription activation, while Sox2 and Egr1 were predicted to regulate repression. Finally, RXRa-RARg regulatory networks were reconstructed through integration of functional co-citations. Our analysis provides a dynamic view of RA signalling during cell differentiation, reveals RA heterodimer dynamics and promiscuity, and predicts decisions that diversify the RA signal into distinct gene-regulatory programs.
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| Overall design |
Transcriptional activity in F9 cells treated with different retinoic acid receptor (RAR) agonists; like all-trans retinoic acid (ATRA), BMS961 (RARg-specific), BMS753 (RARa-specific) or BMS641(RARb-specific); has been evaluated at different time-points (2, 6, 24, 48h) and compared with that found under Ethanol-vehicle treatment conditions (48h treatment).
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| Contributor(s) |
Mendoza-Parra MA, Walia M, Sankar M, Gronemeyer H |
| Citation(s) |
21988834 |
| |
| Submission date |
Jul 10, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Marco Antonio Mendoza-Parra |
| E-mail(s) |
[email protected]
|
| Organization name |
IGBMC
|
| Street address |
1, rue Laurent Fries
|
| City |
Illkirch; Strasbourg |
| ZIP/Postal code |
67400 |
| Country |
France |
| |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE30539 |
Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics |
|
| Relations |
| BioProject |
PRJNA154777 |
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