| Changes in Gene Expression and Estrogen Receptor Cistrome in Mouse Liver Upon Acute E2 Treatment Auteur(s) : Palierne, Gaëlle Fabre, A. J. Solinhac, Romain Le Peron, Christine Avner, Stéphane Lenfant, Françoise Fontaine, Coralie Salbert, Gilles Auteurs secondaires : Institut de Génétique et Développement de Rennes (IGDR) ; Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Institut des Maladies Métaboliques et Cardiovasculaires (I2MC) ; Université Paul Sabatier - Toulouse 3 (UPS) - Hôpital de Rangueil - Institut National de la Santé et de la Recherche Médicale (INSERM) Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Centre National de la Recherche Scientifique, University of Rennes I, Conseil Regional Midi-Pyrenees, Fondation pour la Recherche Medicale, French Government National Infrastructure, Investissements d'Avenir program [ANR-10-INBS-0009], Association pour la Recherche Contre le Cancer, Ligue Contre le Cancer (Equipe Labelisee Ligue), Region Bretagne [CREATE 4793], Agence Nationale pour la Recherche [ANR-09-BLAN-0268-01], Inserm, University of Toulouse III, Faculty of Medecine Toulouse-Rangueil, Fondation de France ANR-10-INBS-09-01/10-INBS-0009, France-Génomique, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010) Éditeur(s) : HAL CCSD Endocrine Society Résumé : International audience Transcriptional regulation by the estrogen receptor-alpha(ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17 beta-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis. Characterization of the chromatin state of ER binding sites (BSs) in mice expressing or not ER demonstrated that ER is not required per se for the establishment and/or maintenance of chromatin modifications at the majority of its BSs. This is presumably a consequence of a strong overlap between ER and hepatocyte nuclear factor 4 alpha BSs. In contrast, 40% of the BSs of the pioneer factor forkhead box protein a (Foxa2) were dependent upon ER expression, and ER expression also affected the distribution of nucleosomes harboring dimethylated lysine 4 of Histone H3 around Foxa2 BSs. We finally show that, in addition to a network of liver-specific transcription factors including CCAAT/enhancer-binding protein and hepatocyte nuclear factor 4 alpha, ER might be required for proper Foxa2 function in this tissue. ISSN: 0888-8809 hal-01357623 https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623 https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/document https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/file/Changes%20in%20gene%20expression%201%20and%20Estrogen%20Receptor_accepted.pdf DOI : 10.1210/me.2015-1311 | Partager
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