The circadian clock: a framework linking metabolism, epigenetics and neuronal function

Abstract

The circadian clock machinery is responsible for biological timekeeping on a systemic level. The central clock system controls peripheral clocks through a number of output cues that synchronize the system as a whole. There is growing evidence that changing cellular metabolic states have important effects on circadian rhythms and can thereby influence neuronal function and disease. Epigenetic control has also been implicated in the modulation of biological timekeeping, and cellular metabolism and epigenetic state seem to be closely linked. We discuss the idea that cellular metabolic state and epigenetic mechanisms might work through the circadian clock to regulate neuronal function and influence disease states.

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Figure 1: Histone modifications and the circadian clock.
Figure 2: A network of clocks and their interplay.
Figure 3: How many clock centres are in the brain?
Figure 4: Linking NAD+ metabolism to circadian clock and sleep.

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Acknowledgements

We thank all members of the Sassone-Corsi laboratory for helpful discussion. Funding for S.M. was provided by the US National Institutes of Health (NIH) postdoctoral fellowship GM097899. Financial support for P.S.-C was provided bythe US NIH (grant AG041504), INSERM (grant 44790) and Sirtris Pharmaceuticals (SP-48984).

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Correspondence to Paolo Sassone-Corsi.

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Masri, S., Sassone-Corsi, P. The circadian clock: a framework linking metabolism, epigenetics and neuronal function. Nat Rev Neurosci 14, 69–75 (2013). https://doi.org/10.1038/nrn3393

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