| First Author | Chatagnon A | Year | 2015 |
| Journal | Nucleic Acids Res | Volume | 43 |
| Issue | 10 | Pages | 4833-54 |
| PubMed ID | 25897113 | Mgi Jnum | J:232661 |
| Mgi Id | MGI:5779769 | Doi | 10.1093/nar/gkv370 |
| Citation | Chatagnon A, et al. (2015) RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements. Nucleic Acids Res 43(10):4833-54 |
| abstractText | In mouse embryonic cells, ligand-activated retinoic acid receptors (RARs) play a key role in inhibiting pluripotency-maintaining genes and 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 h of the RA-induced Primitive Endoderm (PrE) differentiation process in F9 embryonal carcinoma (EC) cells. We show here that this dual regulation is associated with RAR/RXR genomic redistribution during the differentiation process. In-depth analysis of RAR/RXR binding sites occupancy dynamics and composition show that in undifferentiated cells, RAR/RXR interact with genomic regions characterized by binding of pluripotency-associated factors and high prevalence of the non-canonical DR0-containing RA response element. By contrast, in differentiated cells, RAR/RXR bound regions are enriched in functional Sox17 binding sites and are characterized with a higher frequency of the canonical DR5 motif. Our data offer an unprecedentedly detailed view on the action of RA in triggering pluripotent cell differentiation and demonstrate that RAR/RXR action is mediated via two different sets of regulatory regions tightly associated with cell differentiation status. |
