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Simplified presentation of the circadian-feedback loops. The cycle starts with the formation of a CLOCK/BMAL heterodimer that initiates the transcription of the per-, cry-, rora-, and rev-Erbα genes. PER and CRY proteins subsequently inhibit CLOCK/BMAL1 transcription (loop 1), REV-ERBα inhibits Bmal transcription, whereas RORA activates Bmal transcription (loop 2).
