Molecular circadian rhythms in central and peripheral clocks in mammals

The last decade has seen tremendous progress in our understanding of the organization and function of the circadian clock. A number of so-called clock genes were discovered, and these genes and their protein products were shown to organize into feedback loops to give a near 24 h rhythmicity. However, the mechanism is much more complicated. First, many new clock components have been identified, increasing both our understanding and the overall complexity of the mechanism. Second, there is now evidence that transcription may not play a central role in determining the functioning of the clock: the identification of post-translational modifications of the clock proteins has revealed new levels of control. Finally, chromatin remodeling seems to be crucial in the regulation of the expression of major clock components. This review describes the recent advances in our knowledge of the molecular clockwork in mammals; in particular, the contribution of new clock components and of post-transcriptional and post-translational events to circadian timekeeping are discussed.