Abstract
It is now unequivocal that one of the major molecular functions of the circadian clock is to control the timing of chromatin states at clock genes and clock controlled genes (ccg). Recent studies indicate that chromatin regulation is a necessary component of clock-mediated transcriptional oscillations and negative feedback inhibition. Biochemical and molecular genetic approaches in Neurospora, Drosophila, and mammals have revealed a growing list of conserved chromatin-remodeling and chromatin-modifying enzymes that are needed for both the transcriptional activation phase and the inhibition phase. Many of these conserved chromatin factors directly interact with core clock components indicating these are more than just coincident factors. Genome-wide approaches have revealed global rhythms in transcription factor binding, nucleosome density, histone modifications and changes to inter- and intrachromosomal contacts revealing a dynamic genome under circadian control. An emerging theme is that natural antisense transcripts originating from clock genes contribute to rhythmic changes in circadian gene expression, which is controlled in part by regulated transitions between euchromatin and facultative heterochromatin. Moreover, the circadian control of metabolic processes creates rhythms in small metabolites like NAD+ and SAM that serve as cofactors and donors for chromatin-modifying enzymes regulating circadian gene expression. Collectively, research over the past decade has unveiled an exquisitely dynamic genome that is appropriately phased to anticipate oscillating environmental conditions.