Figure 2
From: The role of the circadian clock in rheumatoid arthritis
The molecular clock. CLOCK and BMAL heterodimers activate the transcription of per, cry, rev-erb and ror via E box elements on the promoters. The transcribed PER and CRY proteins form a multimeric complex, enter the nucleus and inhibit CLOCK/BMAL-mediated transcription. The PER/CRY complex is degraded during the night, thereby releasing this inhibitory effect and allowing a new cycle of transcription to begin. REV-ERB and ROR proteins compete for a response element (RORE) on the promoter of bmal, thereby repressing and activating transcription accordingly.