Epigenetic Regulation of Biological Rhythms: An Evolutionary Ancient Molecular Timer

Biological rhythms are pervasive in nature, yet our understanding of the molecular mechanisms that govern timing is far from complete. The rapidly emerging research focus on epigenetic plasticity has revealed a system that is highly dynamic and reversible. In this Opinion, I propose an epigenetic clock model that outlines how molecular modifications, such as DNA methylation, are integral components for timing endogenous biological rhythms. The hypothesis proposed is that an epigenetic clock serves to maintain the period of molecular rhythms via control over the phase of gene transcription and this timing mechanism resides in all cells, from unicellular to complex organisms. The model also provides a novel framework for the timing of epigenetic modifications during the lifespan and transgenerational inheritance of an organism.