Abstract
C/EBPα plays important roles in metabolism as well as in the maintenance of energy homeostasis. Here we describe loss of the circadian oscillation of C/ebpα expression in liver of Clock mutant mice. Reporter assays indicate Clock and Bmal significantly induced C/ebpα gene expression whereas Cry suppressed. Real time reporter assays showed that two mutated E-boxes disrupted C/ebpα promoter dependent-oscillation. Chromatin immunoprecipitation suggests Clock can bind to two E-boxes in the C/ebpα promoter with a circadian manner in vivo. Thus, C/ebpα 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/ebpα pathway in liver.
Highlights
Many organisms display physiological and behavioral rhythms of entrainment to a 24-h cycle of light and darkness
Ebpa mRNA from livers of wild-type and Clock mutant mouse to determine the relationship between the circadian clock and temporal C/ebpa gene expression using RT-PCR (Fig. 1)
The findings suggest that a feedback loop of the molecular circadian clock may regulate the upstream region of C/ ebpa containing these two E-boxes
Summary
Many organisms display physiological and behavioral rhythms of entrainment to a 24-h cycle of light and darkness. CLOCK binds DNA and activates transcription after dimerization with BMAL1 [1,2] by driving the rhythmic transcription of other clock and circadian clockcontrolled genes through an E-box (CACGTG). The mammalian circadian clock is an intracellular, transcriptional-translational mechanism comprising the same molecular components in the suprachiasmatic nucleus and in peripheral cells. Because this endogenous timekeeper interacts with countless biological systems, circadian disruption has significant effects on health; for example, susceptibility to obesity, diabetes and related metabolic syndromes and various types of cancer is increased among long-term shift workers [4]
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