Figure 2.

The molecular clock is regulated by transcription–translation feedback loops. CLOCK/BMAL1 heterodimerize, translocate to the nucleus, and regulate expression of Per/Cry genes. PER/CRY proteins accumulate in the cytoplasm where they heterodimerize and translocate to the nucleus to inhibit CLOCK/BMAL1-driven promotion of their transcription (top). The CLOCK/BMAL1 heterodimer drives expression of ROR and REV-ERB proteins. ROR and REV-ERB proteins translocate to the nucleus and either drive or inhibit BMAL1 expression, respectively (bottom). Created with Biorender.com accessed on 24 July 2023.