While the steady-state behavior of stochastic gene expression with auto-regulation has been extensively studied, its time-dependent behavior has received much less attention. Here, under the assumption of fast promoter switching, we derive and solve a reduced chemical master equation for an auto-regulatory gene circuit with translational bursting and cooperative protein-gene interactions. The analytical expression for the time-dependent probability distribution of protein numbers enables a fast exploration of large swaths of the parameter space. For a unimodal initial distribution, we identify three distinct types of stochastic dynamics: (i) the protein distribution remains unimodal at all times; (ii) the protein distribution becomes bimodal at intermediate times and then reverts back to being unimodal at long times (transient bimodality); and (iii) the protein distribution switches to being bimodal at long times. For each of these, the deterministic model predicts either monostable or bistable behavior, and hence, there exist six dynamical phases in total. We investigate the relationship of the six phases to the transcription rates, the protein binding and unbinding rates, the mean protein burst size, the degree of cooperativity, the relaxation time to the steady state, the protein mean, and the type of feedback loop (positive or negative). We show that transient bimodality is a noise-induced phenomenon that occurs when the protein expression is sufficiently bursty, and we use a theory to estimate the observation time window when it is manifested.
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7 May 2020
Research Article|
May 06 2020
Dynamical phase diagram of an auto-regulating gene in fast switching conditions
Chen Jia
;
Chen Jia
1
Applied and Computational Mathematics Division, Beijing Computational Science Research Center
, Beijing 100193, China
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Ramon Grima
Ramon Grima
a)
2
School of Biological Sciences, University of Edinburgh
, Edinburgh, United Kingdom
a)Author to whom correspondence should be addressed: Ramon.Grima@ed.ac.uk
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a)Author to whom correspondence should be addressed: Ramon.Grima@ed.ac.uk
J. Chem. Phys. 152, 174110 (2020)
Article history
Received:
March 10 2020
Accepted:
April 06 2020
Citation
Chen Jia, Ramon Grima; Dynamical phase diagram of an auto-regulating gene in fast switching conditions. J. Chem. Phys. 7 May 2020; 152 (17): 174110. https://doi.org/10.1063/5.0007221
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