Epigenetic regulation of the molecular clockwork.

Circadian rhythms control a wide range of physiological events in all organisms. Typical of our modern lifestyles is the flexibility to rest, exercise, eat, or socialize at any time of the circadian day or night; yet, these allowances correlate with rising disorders of a metabolic nature, which are thought to be mediated by changes in the molecular events underlying metabolic gene expression. Because the clock confers on gene expression changes in activity that are not necessarily related to changes in DNA sequence, the study of circadian rhythms is inseparable from epigenetics. Increasingly evident is that energy balance at the systems level relies on precise and collaborative circadian timing of epigenetic events within individual cells and tissues of the body. At the center of these rhythms resides the circadian clock machinery, a remarkably well-orchestrated transcription-translation feedback system that incorporates a fluctuating landscape of mRNA expression, protein stability, chromatin state, and metabolite abundance to keep correct time. Understanding more fully the ties that exist between cellular metabolism and the circadian clock at the epigenetic level will produce not only needed insights about circadian physiology but also novel strategies for the pharmacological and nonpharmacological treatment of metabolic disorders.