Figure 1.

Circadian clock mechanism. BMAL1 and CLOCK are basic helix-loop-helix (bHLH)-PAS transcription factors, whose heterodimer transcripts a large number of genes, such as Per, Cry, Rora, Rev-Erb. PER and CRY are circadian clock repressors. They bind to each other and the PER:CRY complex undergoes phosphorylation, which enables translocation into the nucleus, where it can act as a repressor of BMAL1:CLOCK-dependent transcription. The second feedback loop of the circadian clock consists of two proteins, ROR and REV-ERB. ROR belongs to the same bHLH transcriptor factor family. ROR binds to RORE promotor sequence and transcripts circadian activators. The expression of ROR inhibitor (REV-ERB) occurs at the same time as ROR.