TY - JOUR
T1 - Weak coupling between intracellular feedback loops explains dissociation of clock gene dynamics
AU - Schmal, Christoph
AU - Ono, Daisuke
AU - Myung, Jihwan
AU - Pett, J. Patrick
AU - Honma, Sato
AU - Honma, Ken Ichi
AU - Herzel, Hanspeter
AU - Tokuda, Isao T.
N1 - Publisher Copyright:
© 2019 Schmal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/9/12
Y1 - 2019/9/12
N2 - 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.
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.
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U2 - 10.1371/journal.pcbi.1007330
DO - 10.1371/journal.pcbi.1007330
M3 - Article
C2 - 31513579
AN - SCOPUS:85072628364
SN - 1553-734X
VL - 15
SP - e1007330
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 9
M1 - e1007330
ER -