RT Journal Article
SR Electronic
T1 Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 542852
DO 10.1101/542852
A1 Christoph Schmal
A1 Daisuke Ono
A1 Jihwan Myung
A1 J. Patrick Pett
A1 Sato Honma
A1 Ken-Ichi Honma
A1 Hanspeter Herzel
A1 Isao T. Tokuda
YR 2019
UL http://biorxiv.org/content/early/2019/02/06/542852.abstract
AB 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.