RAR/RXR binding dynamics distinguishes pluripotency from differentiation-associated cis-regulatory elements
Transcriptomics Dataset
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General Information
AccessionGSE56893
TitleRAR/RXR binding dynamics distinguishes pluripotency from differentiation-associated cis-regulatory elements
DescriptionIn 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.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56893
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE56893
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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