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Status |
Public on Oct 11, 2011 |
Title |
Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics [ChIP-seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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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 |
RXRa; RARg and RNA Polymerase II chromatin binding has been assessed at five time points; in addition an input control for F9 cells as well as a RXRa ChIP-seq assay from a rxra-/- ko strain has been performed.
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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 |
May 15, 2019 |
Contact name |
Marco Antonio Mendoza-Parra |
E-mail(s) |
marco@igbmc.fr
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Organization name |
IGBMC
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Street address |
1, rue Laurent Fries
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City |
Illkirch; Strasbourg |
ZIP/Postal code |
67400 |
Country |
France |
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Platforms (1) |
GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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Samples (20)
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This SubSeries is part of SuperSeries: |
GSE30539 |
Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics |
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Relations |
SRA |
SRP007613 |
BioProject |
PRJNA154779 |