Fig. 2.

Molecular clock of a mammalian cell. Molecular machinery of the circadian clock is composed of interlocked molecular feedback loops. The core loop is composed of positive elements (CLOCK and BMAL1) and negative elements (PERs and CRYs). The loop is interlocked antiphasic to the Bmal1 loop (positive element: ROR; negative element: REB-ERBα) and in phase with the Dec loop (positive elements: CLOCK and BMAL1; negative elements: DECs). Light-responsive elements such as cAMP response element (CRE), to which phosphorylated CREB binds to induce transcription, exists upstream of Per1, Per2, and Dec1 transcription start sites. Post-transcriptional and post-translational modifications such as ubiquitination and phosphorylation are important for regulating the circadian period