Figure 1.

Schematic representation of the molecular clock. The transactivational complex BMAL1-CLOCK activates genes with E-BOX regulatory sites. PER-CRY complexes reduce this transactivational activity of BMAL1-CLOCK and provide a negative feedback. However, PER2 can also interact with nuclear receptors, for example, PPARα (peroxisome proliferator-activated receptor α) and positively regulate Bmal1 through activation of nuclear receptor response elements (NRE). On the level of transcriptional regulation of Bmal1, there is also competition between RORα and REV-ERBα, providing either transcriptional activation or repression, respectively, by binding to ROR response elements (RORE) and thereby stabilizing the molecular clock [1,10,21,22].