Figure 1:

The core circadian transcriptional-translational feedback loops. The circadian cell-autonomous oscillator is characterized by an intracellular interaction of a handful of core clock components that activate and inhibit each other over approximately 24 hours. These feedback loops are present in virtually all cells of the body and are synchronized by the central pacemakers, the suprachiasmatic nuclei. They are transcriptional-translational because the feedback occurs partly through protein-protein interactions (shown as circles) and partly through activation of gene transcription via E-box, D-box, and RORE promoter elements (shown as rectangles). Gene names are italicized. Bmal1: Brain and Muscle ARNTL-Like 1 (ARNTL, Aryl Hydrocardon Receptor Nuclear Translocator Like). CLOCK: Circadian locomotor output cycles kaput. Cry: Cryptochrome. Per: Period. CK1: Casein kinase 1. Rev-ERBs: Reverse strand of Erb nuclear receptor subfamily. RORs: RAR-related orphan receptors (RAR, retinoid acid receptor).