Figure 1.

Circadian clock proteins and their negative feedback loop. By binding to E-boxes in DNA, the BMAL1-CLOCK heterodimer induces the expression of target genes, including PER and CRY, the protein products of which inhibit the expression of BMAL1 and CLOCK. The lack of BMAL1 and CLOCK inhibits the expression of CRY and PER, causing the cycle to start anew. DEC1 and DEC2 compete with the BMAL1-CLOCK heterodimer for the binding of E-boxes, and are therefore involved in the regulation of expression of the target genes. By binding ROR response elements (ROREs), RORα induces the expression of BMAL1, while REV-ERBα inhibits the expression of BMAL1. The activity of CRY1 is also regulated by its interaction with FBXL proteins, which regulate its degradation.