Circadian Clock Induction

Definition

The circadian timing system efficiently orchestrates the physiology of living organisms to match environmental or imposed 24-h cycles. Most cells in the brain and peripheral tissues contain a molecular clock consisting of at least 12 specific clock genes in mammals. This molecular clock rhythmically controls the transcriptional activity of nearly 10% of the genome, ∼10% of which are proliferation-related genes, over the 24 h. Among the 12 genes which constitute the molecular clock, Per2, Bmal1, and Rev-erbα play a central role. Thus, a null mutation in these genes results in profound alterations of the circadian phenotype. The intracellular clock mechanisms involve interacting positive and negative transcriptional feedback loops that drive recurrent rhythms in the RNA levels of these key components. High levels of Bmal1 mRNA and protein promote the formation of BMAL1:CLOCK heterodimers that bind to the E-box sequences in the promoter of clock genes Per2 and Rev-erbαand...