Article first published online: 19 AUG 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 4, pages 1410–1420, October 2011
How to Cite
Tao, W., Chen, S., Shi, G., Guo, J., Xu, Y. and Liu, C. (2011), SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism. Hepatology, 54: 1410–1420. doi: 10.1002/hep.24514
Potential conflict of interest: Nothing to report.
Supported by grants from the National 973 Program of China (2011CB711000), the National Natural Science Foundation of China (30870928, 30700200), the Research Fund for the Doctoral Program of Higher Education of China (20103207110007), the Fok Ying Tong Education Foundation (121022), the Major Program of Educational Commission of Jiangsu Province (09KJA180004) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
- Issue published online: 27 SEP 2011
- Article first published online: 19 AUG 2011
- Accepted manuscript online: 2 JUL 2011 03:32PM EST
- Manuscript Accepted: 15 JUN 2011
- Manuscript Received: 22 JAN 2011
Many aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism, are under precise control by the mammalian circadian clock. However, the molecular mechanism for coordinate integration of the circadian clock and various metabolic pathways is poorly understood. Here we show that BAF60a, a chromatin-remodeling complex subunit, is rhythmically expressed in the liver of mice. Mice with liver-specific knockdown of BAF60a show abnormalities in the rhythmic expression pattern of clock and metabolic genes and in the circulating metabolite profile. Consistently, knockdown of BAF60a impairs the oscillation of clock genes in serum-shocked HepG2 cells. At the molecular level, BAF60a activates Bmal1 and G6Pase transcription by way of the coactivation of retinoid-related orphan receptor alpha (RORα). In addition, BAF60a is present near ROR response elements (RORE) on the proximal Bmal1 and G6Pase promoters and turns the chromatin structure into the active state. Conclusion: Our data suggest a critical role for BAF60a in the coordinated regulation of hepatic circadian clock and energy metabolism in mammals. (HEPATOLOGY 2011;)