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Vous êtes ici : Accueil / Équipes / Comparative and Integrative Genomics of Organ Development - S.Pantalacci/M. Semon / Publications / RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements.

RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements.

Amandine Chatagnon, Philippe Veber, Valerie Morin, Justin Bedo, Gerard Triqueneaux, Marie Semon, Vincent Laudet, Florence d'Alche-Buc, and Gerard Benoit (2015)

Nucleic Acids Res, 43(10):4833-54.

In mouse embryonic cells, ligand-activated retinoic acid receptors (RARs) play akey 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 DR5motif. 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 withcell differentiation status.

 
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