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

Meredith A. Sommars, Krithika Ramachandran, Madhavi D. Senagolage, Christopher R. Futtner, Derrik M. Germain, Amanda L. Allred, Yasuhiro Omura, Ilya R. Bederman, Grant D. Barish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 PPARa to potently suppress the induction of fasting transcription. Deletion of hepatocyte Bcl6 enhances lipid catabolism and ameliorates highfat- diet-induced steatosis. In Ppara-null mice, hepatocyte Bcl6 ablation restores enhancer activity at PPARa-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.

Original languageEnglish (US)
Article numbere43922
JournaleLife
Volume8
DOIs
StatePublished - Apr 2019

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis'. Together they form a unique fingerprint.

Cite this