Genomics

Dataset Information

7

Transcription profiling by array of mouse F9 embryonal carcinoma cells treated with retinoic acid receptor agonists


ABSTRACT: 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. 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).

ORGANISM(S): Mus musculus  

SUBMITTER: Hinrich Gronemeyer   Martial Sankar  Mannu Walia  Marco A Mendoza-Parra  Marco Antonio Mendoza-Parra 

PROVIDER: E-GEOD-30537 | ArrayExpress | 2011-10-10

SECONDARY ACCESSION(S): GSE30537PRJNA154777

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-30537.README.txt Txt
E-GEOD-30537.idf.txt Idf
E-GEOD-30537.processed.1.zip Processed
E-GEOD-30537.raw.1.zip Raw
E-GEOD-30537.sdrf.txt Txt
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Publications

Dissecting the retinoid-induced differentiation of F9 embryonal stem cells by integrative genomics.

Mendoza-Parra Marco A MA   Walia Mannu M   Sankar Martial M   Gronemeyer Hinrich H  

Molecular systems biology 20111011


Retinoic acid (RA) triggers physiological processes by activating heterodimeric transcription factors (TFs) comprising retinoic acid receptor (RARα, β, γ) and retinoid X receptor (RXRα, β, γ). 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 RARγ and RXRα and correlated them with transcription  ...[more]

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