Periodic perturbation of the bistable kinetics of gene expression

Abstract

Kinetics of gene expression may be bistable or oscillatory due to the feedbacks between the RNA and protein synthesis. In complex genetic networks, kinetic oscillations may influence bistability. Following this line, we have performed a mean-field analysis and Monte Carlo simulations of periodic perturbation of the bistable kinetics of expression of two genes with mutual suppression of the mRNA production due to negative regulation of the gene transcription by protein. The perturbation is realized via modulation of the rate of the mRNA formation. In the mean-field kinetics, the mRNA and protein concentrations repeat themselves during each period. In the stochastic kinetics, this is also the case, provided that the modulation amplitude is small. If the modulation is appreciable, the latter kinetics exhibit new features. Specifically, the model predicts stochastic intermittence of the states of the genes. If the modulation amplitude is close to maximum, the change of the gene states during subsequent perturbation periods occurs fully at random. Taking into account that the model we use is generic, the results obtained are expected to be of interest far beyond the biophysics and biochemistry of gene expression.