May 16, 2018

Modulation of dynamic modes by interplay between positive and negative feedback loops in gene regulatory networks

Physical Review. E
Liu-Suo WangWei Wang

Abstract

A positive and a negative feedback loop can induce bistability and oscillation, respectively, in biological networks. Nevertheless, they are frequently interlinked to perform more elaborate functions in many gene regulatory networks. Coupled positive and negative feedback loops may exhibit either oscillation or bistability depending on the intensity of the stimulus in some particular networks. It is less understood how the transition between the two dynamic modes is modulated by the positive and negative feedback loops. We developed an abstract model of such systems, largely based on the core p53 pathway, to explore the mechanism for the transformation of dynamic behaviors. Our results show that enhancing the positive feedback may promote or suppress oscillations depending on the strength of both feedback loops. We found that the system oscillates with low amplitudes in response to a moderate stimulus and switches to the on state upon a strong stimulus. When the positive feedback is activated much later than the negative one in response to a strong stimulus, the system exhibits long-term oscillations before switching to the on state. We explain this intriguing phenomenon using quasistatic approximation. Moreover, early switchin...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
TP53
Protein p53
Loop
Gene Regulatory Networks
Feedback, Biochemical
Core
C1orf51 gene
Oscillations
Brain Waves

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