The circadian clock transcriptional complex: metabolic feedback intersects with epigenetic control

Chromatin remodeling is a prerequisite for most nuclear functions, including transcription, silencing, and DNA replication. Accumulating evidence shows that many physiological processes require highly sophisticated events of chromatin remodeling. Recent findings have linked cellular metabolism, epigenetic state, and the circadian clock. The control of a large variety of neuronal, behavioral, and physiological responses follows diurnal rhythms. This is possible through a transcriptional regulatory network that governs a significant portion of the genome. The harmonic oscillation of gene expression is paralleled by critical events of chromatin remodeling that appear to provide specificity and plasticity in circadian regulation. Accumulating evidence shows that the circadian epigenome appears to share intimate links with cellular metabolic processes. These notions indicate that the circadian epigenome might integrate tissue specificity within biological pacemakers, bridging systems physiology to metabolic control. This review highlights several advances related to the circadian epigenome, the contribution of NAD+ as a critical signaling metabolite, and its effects on epigenetic state, followed by more recent reports on circadian metabolomics analyses.