RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements
2015
Chatagnon, Amandine | Veber, Philippe | Morin, Valérie | Bedő,, Justin | Triqueneaux, Gérard | Sémon, Marie | Laudet, Vincent | d'Alché-Buc, Florence | Benoît,, Gérard | Institut de Génomique Fonctionnelle de Lyon (IGFL) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Centre National de la Recherche Scientifique (CNRS) | Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS) | Plateforme de Biologie Moĺeculaire, IBP ; Centre Hospitalier Universitaire [CHU Grenoble] (CHUGA) | Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS) | Informatique, Biologie Intégrative et Systèmes Complexes (IBISC) ; Université d'Évry-Val-d'Essonne (UEVE) | Fondation pour la Recherche Medicale; Agence Nationale pour la Recherche (ANR-09-SYSC-009-02; ANR-2011-BSV8-023-02); Institut National du Cancer (PLBIO08-083)
International audience
Mostrar más [+] Menos [-]Inglés. 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.
Mostrar más [+] Menos [-]Palabras clave de AGROVOC
Información bibliográfica
Este registro bibliográfico ha sido proporcionado por Institut national de la recherche agronomique