Fig. 1.

A schematic view of the core molecular feedback loop that sits at the heart of the mammalian pacemaker. The definition of circadian time pivots around the activation of Per and Cry genes by Clock/Bmal1 heterodimers (acting at E-box enhancer sequences), alternating with repression of the same genes by their protein products. Clock-controlled output genes carrying E-boxes are also subject to daily activation and repression, generating downstream transcriptional cascades that ultimately encode circadian cycles of physiology and behaviour.