Figure 1.

Schematic illustration of the molecular circadian clock. BMAL1: CLOCK heterodimer binds to E-box present on the promoter region of Per and Cry. Then PER together with CRY inhibit their own transcript. The second feedback loop involves the transactivation of the Rev-Erbα, Rev-Erbβ, and Rora genes by CLOCK/BMAL1. Then REV-ERBα, REV-ERBβ and RORA compete for binding to RRE elements in the Bmal1 promoter, driving a daily rhythm of Bmal1 transcription and the second feedback loop. These feedback loops generate a 24-hour rhythmic oscillation.