Molecular components of the mammalian circadian clock
1 Department of Neurobiology and Physiology, 2 Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208, USA and 3 Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3
* To whom correspondence should be addressed at: Howard Hughes Medical Institute, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA. Tel: +1 8474914598; Fax: +1 8474914600; Email: j-takahashi{at}northwestern.edu
Received July 14, 2006; Accepted July 28, 2006
Circadian rhythms are 
24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional–translational autoregulatory loop generates molecular oscillations of ‘clock genes’ at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.
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