Molecular Analysis of Mammalian Circadian Rhythms

In mammals, a master circadian “clock” resides in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN clock is composed of multiple, single-cell circadian oscillators, which, when synchronized, generate coordinated circadian outputs that regulate overt rhythms. Eight clock genes have been cloned that are involved in interacting transcriptional-/translational-feedback loops that compose the molecular clockwork. The daily light-dark cycle ultimately impinges on the control of two clock genes that reset the core clock mechanism in the SCN. Clock-controlled genes are also generated by the central clock mechanism, but their protein products transduce downstream effects. Peripheral oscillators are controlled by the SCN and provide local control of overt rhythm expression. Greater understanding of the cellular and molecular mechanisms of the SCN clockwork provides opportunities for pharmacological manipulation of circadian timing.