Circadian Clocks Modulate Metabolism and Cellular Transformation via Complex Transcription Networks

Circadian clocks modulate a wide variety of cellular and physiological functions including metabolism and genome protection in a time-of-day dependent manner. Mammalian circadian clocks involve a transcription and translation feedback loop in which the transcription factors Clock and Bmal1 drive expression of period (Per1-3) and cryptochrome (Cry1,2) repressors, which inhibit Clock:Bmal1, resulting in oscillating transcription. My laboratory has discovered several pathways by which Cry1 and Cry2 mediate circadian responses to extracellular stimuli by regulating the activity of transcription factors, including several nuclear hormone receptors. We have also developed tools to elucidate the pathways by which Cry1 and Cry2 integrate extracellular signals to effect transcriptional networks that alter metabolic and proliferative capacity.