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Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα.
Ratman, Dariusz; Mylka, Viacheslav; Bougarne, Nadia; Pawlak, Michal; Caron, Sandrine; Hennuyer, Nathalie; Paumelle, Réjane; De Cauwer, Lode; Thommis, Jonathan; Rider, Mark H; Libert, Claude; Lievens, Sam; Tavernier, Jan; Staels, Bart; De Bosscher, Karolien.
Afiliación
  • Ratman D; Receptor Research Laboratories, Nuclear Receptor Lab, Medical Biotechnology Center, VIB, 9000 Ghent, Belgium.
  • Mylka V; Department of Biochemistry, Ghent University, 9000 Ghent, Belgium.
  • Bougarne N; Receptor Research Laboratories, Nuclear Receptor Lab, Medical Biotechnology Center, VIB, 9000 Ghent, Belgium.
  • Pawlak M; Department of Biochemistry, Ghent University, 9000 Ghent, Belgium.
  • Caron S; Receptor Research Laboratories, Nuclear Receptor Lab, Medical Biotechnology Center, VIB, 9000 Ghent, Belgium.
  • Hennuyer N; Department of Biochemistry, Ghent University, 9000 Ghent, Belgium.
  • Paumelle R; UNIV LILLE, 59000 Lille, France.
  • De Cauwer L; INSERM UMR 1011, 59000 Lille, France.
  • Thommis J; European Genomic Institute for Diabetes E.G.I.D., FR 3508, 59000 Lille, France.
  • Rider MH; Institut Pasteur de Lille, 59000 Lille, France.
  • Libert C; UNIV LILLE, 59000 Lille, France.
  • Lievens S; INSERM UMR 1011, 59000 Lille, France.
  • Tavernier J; European Genomic Institute for Diabetes E.G.I.D., FR 3508, 59000 Lille, France.
  • Staels B; Institut Pasteur de Lille, 59000 Lille, France.
  • De Bosscher K; UNIV LILLE, 59000 Lille, France.
Nucleic Acids Res ; 44(22): 10539-10553, 2016 12 15.
Article en En | MEDLINE | ID: mdl-27576532
Adaptation to fasting involves both Glucocorticoid Receptor (GRα) and Peroxisome Proliferator-Activated Receptor α (PPARα) activation. Given both receptors can physically interact we investigated the possibility of a genome-wide cross-talk between activated GR and PPARα, using ChIP- and RNA-seq in primary hepatocytes. Our data reveal extensive chromatin co-localization of both factors with cooperative induction of genes controlling lipid/glucose metabolism. Key GR/PPAR co-controlled genes switched from transcriptional antagonism to cooperativity when moving from short to prolonged hepatocyte fasting, a phenomenon coinciding with gene promoter recruitment of phosphorylated AMP-activated protein kinase (AMPK) and blocked by its pharmacological inhibition. In vitro interaction studies support trimeric complex formation between GR, PPARα and phospho-AMPK. Long-term fasting in mice showed enhanced phosphorylation of liver AMPK and GRα Ser211. Phospho-AMPK chromatin recruitment at liver target genes, observed upon prolonged fasting in mice, is dampened by refeeding. Taken together, our results identify phospho-AMPK as a molecular switch able to cooperate with nuclear receptors at the chromatin level and reveal a novel adaptation mechanism to prolonged fasting.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cromatina / Receptores de Glucocorticoides / Adenilato Quinasa / PPAR alfa Tipo de estudio: Prognostic_studies Idioma: En Revista: Nucleic Acids Res Año: 2016 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cromatina / Receptores de Glucocorticoides / Adenilato Quinasa / PPAR alfa Tipo de estudio: Prognostic_studies Idioma: En Revista: Nucleic Acids Res Año: 2016 Tipo del documento: Article