The Circadian Binding Of Clock Protein To The Promoter Of C/Ebp Alpha Gene In Mouse Cells

C/ebp alpha plays important roles in metabolism as well as in the maintenance of energy homeostasis. Here we describe loss of the circadian oscillation of C/ebp alpha expression in liver of Clock mutant mice. Reporter assays indicate Clock and Bmal significantly induced C/ebp alpha gene expression whereas Cry suppressed. Real time reporter assays showed that two mutated E-boxes disrupted C/ebp alpha promoter dependent-oscillation. Chromatin immunoprecipitation suggests Clock can bind to two E-boxes in the C/ebp alpha promoter with a circadian manner in vivo. Thus, C/ebp alpha gene transcription is under circadian control of a core clock component, Clock. The data suggests that circadian disturbances may affect metabolic abnormalities through the C/ebp alpha pathway in liver.