Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis


Journal article


Meredith A. Sommars, Krithika Ramachandran, Madhavi D. Senagolage, C. Futtner, Derrik M Germain, Amanda L. Allred, Yasuhiro Omura, I. Bederman, G. Barish
eLife, 2019

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APA   Click to copy
Sommars, M. A., Ramachandran, K., Senagolage, M. D., Futtner, C., Germain, D. M., Allred, A. L., … Barish, G. (2019). Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis. ELife.


Chicago/Turabian   Click to copy
Sommars, Meredith A., Krithika Ramachandran, Madhavi D. Senagolage, C. Futtner, Derrik M Germain, Amanda L. Allred, Yasuhiro Omura, I. Bederman, and G. Barish. “Dynamic Repression by BCL6 Controls the Genome-Wide Liver Response to Fasting and Steatosis.” eLife (2019).


MLA   Click to copy
Sommars, Meredith A., et al. “Dynamic Repression by BCL6 Controls the Genome-Wide Liver Response to Fasting and Steatosis.” ELife, 2019.


BibTeX   Click to copy

@article{meredith2019a,
  title = {Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis},
  year = {2019},
  journal = {eLife},
  author = {Sommars, Meredith A. and Ramachandran, Krithika and Senagolage, Madhavi D. and Futtner, C. and Germain, Derrik M and Allred, Amanda L. and Omura, Yasuhiro and Bederman, I. and Barish, G.}
}

Abstract

Transcription is tightly regulated to maintain energy homeostasis during periods of feeding or fasting, but the molecular factors that control these alternating gene programs are incompletely understood. Here, we find that the B cell lymphoma 6 (BCL6) repressor is enriched in the fed state and converges genome-wide with PPARα to potently suppress the induction of fasting transcription. Deletion of hepatocyte Bcl6 enhances lipid catabolism and ameliorates high-fat-diet-induced steatosis. In Ppara-null mice, hepatocyte Bcl6 ablation restores enhancer activity at PPARα-dependent genes and overcomes defective fasting-induced fatty acid oxidation and lipid accumulation. Together, these findings identify BCL6 as a negative regulator of oxidative metabolism and reveal that alternating recruitment of repressive and activating transcription factors to shared cis-regulatory regions dictates hepatic lipid handling.