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Significance Almost all living organisms have evolved circadian clocks to tell time. Circadian clocks regulate ∼24-h oscillations in gene expression and control much of our behavior and physiology. Here, we reveal the surprisingly sophisticated spatiotemporal organization of core clock proteins and genes over the circadian cycle and its critical role in circadian clock function. We show thatDrosophila clock proteins are concentrated in a few discrete foci and that they play a key role in positioning the core clock genes close to the nuclear envelope precisely during the repression phase to control circadian rhythms. These studies provide fundamental insights into cellular mechanisms of circadian rhythms and establish direct links between nuclear organization and circadian rhythms.

Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms