Figure 1.

Clock-BMAL1 complex activity during a day cycle. At sunrise, CLOCK-BMAL1 promotes the beginning of the circadian clock by binding to the enhancer box (E-box) regions of target circadian clock genes (CG) and increasing their transcription. During the day, the cellular levels of clock proteins such as PER 1/2/3, CRY 1/2, TIM, and REV-ERB continue to rise; at the day’s end, their association with casein kinase 1 epsilon (CK1ε) facilitates transportation into the cell nucleus, where circadian clock gene proteins have a negative feedback effect on the activity of the CLOCK-BMAL1 complex. The suppressive effect of the PER-CRY-CK1ε complex on transcription factors leads to their inhibition of their own transcription, and a consequent decrease in the complex’s cell levels during the night and until dawn, after which the activity of CLOCK-BMAL1 is once again unimpaired, and the circadian clock restarts. Created with BioRender.com.