Figure 1.

A general model of the canonical circadian molecular feedback loop. CLOCK and BMAL1 promote the expression of clock-controlled genes (ccgs), and genes encoding PERs and CRYs. PER (1, 2, 3) and CRY (1, 2) are progressively accumulated in the cytoplasm and subsequently shuttled into the nucleus as hetero/homodimers. Here, they repress the CLOCK: BMAL1 transactivation. Rev-erb and Ror gene expression is also regulated by CLOCK: BMAL1 transactivation. Both their protein products, REV-ERB, and ROR, compete for the ROR responsive elements (ROREs) within the Bmal1 promoter driving its circadian gene expression. TSS, Transcriptional Start Site.