Figure 2.

Diagram of the molecular basis of the circadian sleep-wake cycle. The BMAL1 and CLOCK genes are transcribed to proteins BMAL1 and CLOCK, which combine to create a transcription factor BMAL1/CLOCK, which facilitates transcription of the PER and CRY proteins from their respective genes. PER and CRY form a dimer in the cytoplasm that gradually increases in concentration in the cytoplasm and reenters the nucleus, providing negative feedback. CK1ε CSNK1E facilitates degradation of PER. ROR1 and REV-ERBα regulate BMAL1. (Adapted with permission from Lowrey et al.⁸³)