Fluctuations-induced switch in the gene transcriptional regulatory system

Abstract

Based on the kinetic model of genetic regulation system proposed by Am. J. Physiol. 274, c531 (1998)], the effects of fluctuations in the degradation reaction rate and the synthesis reaction rate of the transcription factor have been investigated through numerical computation and analysis theory. In the case of uncorrelated noises, it is shown that only the fluctuation of degradation reaction rate can induce a switch process, and the mean first passage time (MFPT) from the high concentration state to the low concentration one is decreased when the noise intensity of degradation reaction rate is increased. In the case of correlations between noises, a switch process can also be induced by the cross-correlation intensity between noises and by the fluctuation of the synthesis reaction rate in the genetic regulatory system. It is found that, under large cross-correlation intensity, a successive switch process (i.e., "on" --> "off" --> "on," which we call the reentrance transition or twice switch ) occurs with an increase of noise intensities, and a critical noise intensity exists at which the MFPT of the switch process is the largest. While the system is initially in the high concentration state with an increase of the cross correlation, the stationary probability distribution (SPD) of the transcription factor activator monomer concentration at the low concentration state is increased, yet the MFPT is increased due to the decreasing of the SPD of the transient states between the two steady stable states.

Emergent bistability: Effects of additive and multiplicative noise

“…The corresponding FP equation is a rate equation for the probability distribution [27,28]. Noise in the form of random fluctuations has a non-trivial effect on the gene expression dynamics involving positive feedback [22,[30][31][32]. In this paper, we investigate the effects of additive and multiplicative noise on the dynamics, described by Eq.…”

Time delay-accelerated transition of gene switch and -enhanced stochastic resonance in a bistable gene regulatory model

“…and R bas =0.4, the stable steady states are x − ≈0.62685 and x + ≈4.28343, and the unstable steady state is x u ≈1.48971 as shown in Fig.3 [23]. …”

“…Moreover, the effects of macromolecular transport and stochastic fluctuations on dynamics of genetic regulatory systems are investigated. Liu [23]et al have studied the effects of the correlation between the noise of the decomposed rate k d and the noise of the synthesis rate R bas . They found that a successive switch process (i.e., "on"→"off"→"on", which we call the reentrance transition or twice switch) occurs with increasing the noise intensities, and a critical noise intensity exists at which the mean first passage time of the switch process is the largest.…”

“…As the basic principles of genetic regulation have been characterized, it has become increasingly evident that nonlinear interactions, positive and negative feedback within signaling pathways, time delays, protein oligomerization, and crosstalk between different pathways need to be considered to fully understand genetic regulation [20], [21], [22], [23], [24], [25], [26]. Smolen et al have introduced a simple genetic regulatory model that incorporate known features of genetic regulatory using an explicitly mathematical dynamic systems approach [20], [21].…”

Influences of a periodic signal on a noisy synthetic gene network

“…In research on gene networks, attention has largely been paid to the effects of the intracellular or extracellular noise on gene networks, and analyses of cellular interactions and communication have also been reported [37][38][39]. It has been demonstrated that stochastic effects play a major role in several macroscopic gene regulatory phenomena [40][41][42][43][44].…”