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Series GSE56893 Query DataSets for GSE56893
Status Public on Apr 17, 2015
Title RAR/RXR binding dynamics distinguishes pluripotency from differentiation-associated cis-regulatory elements
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary In mouse embryonic cells, a retinoic acid (RA) stimulation triggers a massive change of gene expression leading the pluripotent, proliferating cells to a lineage-specific differentiation process. The retinoic acid receptor (RAR) plays a key role in this response by inhibiting pluripotency-maintaining genes and simultaneously activating some major actors of cell differentiation. To investigate the mechanism underlying this dual regulation, we performed joint RAR/RXR ChIP-seq and mRNA-seq time series during the first 48 hours of the RA-induced Primitive Endoderm differentiation process in F9 embryonic carcinoma cells. We detected significantly more RAR/RXR binding regions than previous studies and identified among them a handful of typical binding intensity patterns during differentiation. We demonstrate that these patterns are correlated with the coincidental binding of essential transcription factors (TFs) for pluripotency maintenance or PrE differentiation of embryonic stem (ES) cells, as well as the presence of variants of RAR binding motifs. Most importantly, early-bound regions coincide with pluripotency-associated transcription factor binding in ES (like Pou5f1, Sox2, Esrrb and Nr5a2) and display an increased frequency of the DR0 type RAR binding motifs; late-bound sites are associated to the PrE marker Sox17 and are enriched in the canonical DR5 binding motif. Our data offer an unprecedently detailed view on the action of RA in triggering pluripotent cell differentiation. Altogether, this work sheds light on the relocation of RAR/RXR binding sites throughout differentiation, and shows how RAR/RXR progressively shift from DR0 enriched regions, which were specifically identified in undifferentiated models, to canonical RAR binding sites containing loci.
Overall design Time course (0, 2, 6, 12, 24, 48h) after stimulation of F9 cultured cells by retinoic acid: PanRAR and PanRXR ChIP-seq at 0, 2, 24 and 48h (no replicate); WCE-seq at 0h (no replicate); mRNA-seq at 0, 6, 12, 24, 48h (2 replicates except for time 0h, 4 replicates). Additionally, a control time course (culture in DMSO) sampled at 24 and 48h (no replicates).
Contributor(s) Chatagnon A, Veber P, Bedo J, Morin V, Triqueneaux G, Sémon M, Laudet V, d'Alché-Buc F, Benoit G
Citation(s) 25897113
Submission date Apr 17, 2014
Last update date May 15, 2019
Contact name Philippe Veber
Organization name CNRS
Lab Laboratoire de Biométrie et Biologie Évolutive.
Street address 16 rue Raphael Dubois
City Villeurbanne
ZIP/Postal code 69622
Country France
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (23)
GSM1370729 WCE 0h
GSM1370730 ChIP RAR 0h
GSM1370731 ChIP RXR 0h
BioProject PRJNA244877
SRA SRP041261

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE56893_Gene_expression.xlsx.gz 813.3 Kb (ftp)(http) XLSX
GSE56893_RAR_RXR_regions.bed.gz 120.6 Kb (ftp)(http) BED
GSE56893_RAR_RXR_regions.xlsx.gz 4.2 Mb (ftp)(http) XLSX
GSE56893_RAW.tar 1.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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