CHRONO integrates behavioral stress and epigenetic control of metabolism.

Circadian rhythms are a critical part of the body's homeostatic mechanisms. These rhythms repeat with a cycle-length of approximately 24 h and are generated by a transcriptional-translational feedback loop. These rhythms are critical for proper behavioral, physiological, and molecular functions. CHRONO, a novel circadian clock gene, forms a complex with other clock proteins and modulates the circadian machinery. CHRONO also interacts with histone deacetylase (HDAC) to modulate the epigenetic status of the transcriptional regulation. Chrono knockout mice display a longer period of circadian behavior and an elevated stress response. This paper reviews the molecular function of CHRONO with a focus on epigenetic regulation and speculates on the possible function of CHRONO in physiological processes. Key messages Chrono is a circadian clock gene whose transcription exhibits a robust circadian oscillation. CHRONO is a repressor of circadian transcriptional/translational feedback loops. CHRONO may function to link epigenetic control mechanisms to stress responses.