Sirtuins and the Circadian Clock: Epigenetic and Metabolic Crosstalk

Mammalian sirtuins and the circadian clock appear to be intimately linked. The circadian clock is able to modulate the activity of SIRT1 while SIRT1 also deacetylates specific elements of the clock machinery and modifies histones to regulate gene expression. In this chapter, we review the current understanding of the field on the interrelationship between SIRT1 and the circadian clock machinery, how this regulation occurs, and what other possible functions the sirtuins could have in circadian biology. This chapter also discusses the critical metabolic cues that are in place to regulate enzymes involved in histone modifications and subsequent regulation of gene expression. The role of the clock in regulating metabolic state of the cell is also a concept that will be explored, as the clock-dependent control over metabolism is far more extensive than originally thought. The concept that metabolism and epigenetics are closely linked opens new directions that need to be explored in terms of circadian metabolic regulation and how this modulates a host of epigenetic modifying enzymes and chromatin remodelers.