Bmal1/Clock complex activates transcription of genes containing E-box sequences in their promoters. Among these are Per1/2 and Cry1/2, which following dimerization can inhibit the activity of the Bmal1/Clock complex. Rev-Erb and Ror provide an additional stabilizing loop to fine-tune the expression of Bmal1. In addition to E-boxes, other clock regulatory elements (such as ROREs and D-boxes) are commonly found in the promoters of CCGs.
Disruptions of daily rhythms of the body’s master internal clock provide insight into the role of the brain’s internal time keeping system in the development of mood disorders, such as bipolar disorder and major depressive disorder MDD, which have been associated with disturbed daily (circadian) rhythms...
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