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Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα

(2016) NUCLEIC ACIDS RESEARCH. 44(22). p.10539-10553
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Abstract
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.
Keywords
FATTY-ACID OXIDATION, NF-KAPPA-B, DEPENDENT PROTEIN-KINASE, RECEPTOR-ALPHA, GLUCOCORTICOID-RECEPTOR, SKELETAL-MUSCLE, TRANSCRIPTION FACTOR, HEPATOMA-CELLS, BETA-OXIDATION, ENERGY SENSOR

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Chicago
Ratman, Dariusz, Viacheslav Mylka, Nadia Bougarne, Michal Pawlak, Sandrine Caron, Nathalie Hennuyer, Réjane Paumelle, et al. 2016. “Chromatin Recruitment of Activated AMPK Drives Fasting Response Genes Co-controlled by GR and PPARα.” Nucleic Acids Research 44 (22): 10539–10553.
APA
Ratman, D., Mylka, V., Bougarne, N., Pawlak, M., Caron, S., Hennuyer, N., Paumelle, R., et al. (2016). Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα. NUCLEIC ACIDS RESEARCH, 44(22), 10539–10553.
Vancouver
1.
Ratman D, Mylka V, Bougarne N, Pawlak M, Caron S, Hennuyer N, et al. Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα. NUCLEIC ACIDS RESEARCH. 2016;44(22):10539–53.
MLA
Ratman, Dariusz, Viacheslav Mylka, Nadia Bougarne, et al. “Chromatin Recruitment of Activated AMPK Drives Fasting Response Genes Co-controlled by GR and PPARα.” NUCLEIC ACIDS RESEARCH 44.22 (2016): 10539–10553. Print.
@article{8157311,
  abstract     = {Adaptation to fasting involves both Glucocorticoid Receptor (GR\ensuremath{\alpha}) and Peroxisome Proliferator-Activated Receptor \ensuremath{\alpha} (PPAR\ensuremath{\alpha}) activation. Given both receptors can physically interact we investigated the possibility of a genome-wide cross-talk between activated GR and PPAR\ensuremath{\alpha}, 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, PPAR\ensuremath{\alpha} and phospho-AMPK. Long-term fasting in mice showed enhanced phosphorylation of liver AMPK and GR\ensuremath{\alpha} 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.},
  author       = {Ratman, Dariusz and Mylka, Viacheslav and Bougarne, Nadia and Pawlak, Michal and Caron, Sandrine and Hennuyer, Nathalie and Paumelle, R{\'e}jane and De Cauwer, Lode and Thommis, Jonathan and Rider, Mark H and Libert, Claude and Lievens, Sam and Tavernier, Jan and Staels, Bart and De Bosscher, Karolien},
  issn         = {0305-1048},
  journal      = {NUCLEIC ACIDS RESEARCH},
  language     = {eng},
  number       = {22},
  pages        = {10539--10553},
  title        = {Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPAR\ensuremath{\alpha}},
  url          = {http://dx.doi.org/10.1093/nar/gkw742},
  volume       = {44},
  year         = {2016},
}

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