SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism
Hepatology (2011), 54: 1410-1420.，-0001，（）：
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 via the coactivation of RORα. In addition, BAF60a is present near RORE on the proximal Bmal1 and G6Pase promoters and turns the chromatin structure into active state. Conclusion: Our data suggest a critical role for BAF60a in the coordinate regulation of hepatic circadian clock and energy metabolism in mammals.