Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis
Year: 2019
Type: article
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.
Source: eLife
DOI: 10.7554/elife.43922
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: American Diabetes Association, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Integrative Genomics, Epigenomics and Bioinformatics Analyses of Human Uterine Fibroids, Repressor-PPAR Interactions in Inflammation and Atherosclerosis, Nuclear Repressors in Genomic Control of Healthful Obesity, G8516683306, Cellular and Molecular Basis of Disease Training Program, The Robert H. Lurie Comprehensive Cancer Center
OpenAlex ID: W2936708687