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bioRxiv · 10.1101/542852

Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics

Schmal, C.·Ono, D.·Myung, J.·Pett, J. P.·Honma, S.·Honma, K.-I.·Herzel, H.·Tokuda, I. T.
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Abstract

Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this \"presumably transient\" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.

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Schmal, C., Ono, D., Myung, J., Pett, J. P., Honma, S., Honma, K.-I., Herzel, H., Tokuda, I. T.. 2019-02-06. Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics. https://doi.org/10.1101/542852

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