SIRT1 is a circadian deacetylase for core clock components

Abstract

The transcriptional activator CLOCK is a histone acetyltransferase that is required for the circadian expression of many genes. Asher et al. (2008) and Nakahata et al. (2008) now demonstrate that the NAD(+)-dependent enzyme SIRT1 functions as a histone deacetylase that counteracts the activity of CLOCK. These results broaden our understanding of the impact of cellular metabolism on the circadian system.

Figure 1. The Circadian Rhythm of Acetylation and Deacetylation

During the activation phase, CLOCK-BMAL1 is associated with the E-box promoter element and CLOCK mediates acetylation of histone tails. BMAL1 then becomes acetylated and recruits PER2-CRY1. PER2 is acetylated and curtails the activation phase. Systematic NAD⁺-dependent deacetylation by SIRT of histones, BMAL1, and finally PER2 facilitates the establishment of a repressive chromatin state. For simplicity, SIRT1 is shown only when active.