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Coordination of circadian timing in mammals

Abstract

Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.

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Figure 1: The mammalian circadian timing system is a hierarchy of dispersed oscillators.
Figure 2: Mammalian circadian clockwork model.
Figure 3: CLOCK–BMAL1 heterodimers remain bound to E boxes over the circadian cycle.
Figure 4: New visual pathway from retina to the SCN.
Figure 5: Mechanisms from SCN to clock-controlled gene expression in liver.

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Acknowledgements

We thank members of the Reppert laboratory for contributing to the ideas presented in this review, and U. Schibler for sharing data before publication. This work was supported by grants from the NIH and DARPA.

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Correspondence to Steven M. Reppert.

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Reppert, S., Weaver, D. Coordination of circadian timing in mammals. Nature 418, 935–941 (2002). https://doi.org/10.1038/nature00965

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