rev-erbα participates in circadian srebp signaling and bile acid homeostasisrev-erbα参与生理,如信号和胆汁酸体内平衡.pdfVIP

REV-ERBa Participates in Circadian SREBP Signaling and Bile Acid Homeostasis 1 2 1 1 ˆ 1¤ Gwendal Le Martelot , Thierry Claudel , David Gatfield , Olivier Schaad , Benoıt Kornmann , Giuseppe 3 3 1 Lo Sasso , Antonio Moschetta , Ueli Schibler * 1 Department of Molecular Biology and NCCR Frontiers in Genetics, Sciences III, University of Geneva, Geneva, Switzerland, 2 Laboratory of Experimental and Molecular Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria, 3 Laboratory of Lipid Metabolism and Cancer, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti) and Clinica Medica Murri, University of Bari, Italy Abstract In mammals, many aspects of behavior and physiology, and in particular cellular metabolism, are coordinated by the circadian timing system. Molecular clocks are thought to rely on negative feedback loops in clock gene expression that engender oscillations in the accumulation of transcriptional regulatory proteins, such as the orphan receptor REV-ERBa. Circadian transcription factors then drive daily rhythms in the expression of clock-controlled output genes, for example genes encoding enzymes and regulators of cellular metabolism. To gain insight into clock output functions of REV-ERBa, we carried out genome-wide transcriptome profiling experiments with liver RNA from wild-type mice, Rev-erba knock-out mice, or REV-ERBa overexpressing mice. On the basis of these genetic loss- and gain-of-function experiments, we concluded that REV-ERBa participates in the circadian modulation of sterol regulatory element-binding protein (SREBP) activi