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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
Author
Organization
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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MLA
Ratman, Dariusz, et al. “Chromatin Recruitment of Activated AMPK Drives Fasting Response Genes Co-Controlled by GR and PPARα.” NUCLEIC ACIDS RESEARCH, vol. 44, no. 22, 2016, pp. 10539–53, doi:10.1093/nar/gkw742.
APA
Ratman, D., Mylka, V., Bougarne, N., Pawlak, M., Caron, S., Hennuyer, N., … De Bosscher, K. (2016). Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα. NUCLEIC ACIDS RESEARCH, 44(22), 10539–10553. https://doi.org/10.1093/nar/gkw742
Chicago author-date
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): 10539–53. https://doi.org/10.1093/nar/gkw742.
Chicago author-date (all authors)
Ratman, Dariusz, Viacheslav Mylka, Nadia Bougarne, Michal Pawlak, Sandrine Caron, Nathalie Hennuyer, Réjane Paumelle, Lode De Cauwer, Jonathan Thommis, Mark H Rider, Claude Libert, Sam Lievens, Jan Tavernier, Bart Staels, and Karolien De Bosscher. 2016. “Chromatin Recruitment of Activated AMPK Drives Fasting Response Genes Co-Controlled by GR and PPARα.” NUCLEIC ACIDS RESEARCH 44 (22): 10539–10553. doi:10.1093/nar/gkw742.
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.
IEEE
[1]
D. Ratman et al., “Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα,” NUCLEIC ACIDS RESEARCH, vol. 44, no. 22, pp. 10539–10553, 2016.
@article{8157311,
  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.}},
  author       = {{Ratman, Dariusz and Mylka, Viacheslav and Bougarne, Nadia and Pawlak, Michal and Caron, Sandrine and Hennuyer, Nathalie and Paumelle, Réjane 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}},
  keywords     = {{FATTY-ACID OXIDATION,NF-KAPPA-B,DEPENDENT PROTEIN-KINASE,RECEPTOR-ALPHA,GLUCOCORTICOID-RECEPTOR,SKELETAL-MUSCLE,TRANSCRIPTION FACTOR,HEPATOMA-CELLS,BETA-OXIDATION,ENERGY SENSOR}},
  language     = {{eng}},
  number       = {{22}},
  pages        = {{10539--10553}},
  title        = {{Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα}},
  url          = {{http://dx.doi.org/10.1093/nar/gkw742}},
  volume       = {{44}},
  year         = {{2016}},
}

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