Gene switching rate determines response to extrinsic perturbations in a transcriptional network motif

TL;DR

This study explores how gene switching rates influence the response of transcriptional networks to extrinsic bounded noise, revealing phase transitions dependent on switching speed, noise intensity, and cell size.

Contribution

It introduces a detailed analysis of gene switching dynamics under realistic bounded extrinsic noise, highlighting their role in network response and phase transitions.

Findings

Fast gene switching leads to irreversible noise-induced phase transitions.

Slow gene switching prevents first order transitions.

Cell size and noise autocorrelation influence transition types.

Abstract

It is well-known that gene activation/deactivation dynamics may be a major source of randomness in genetic networks, also in the case of large concentrations of the transcription factors. In this work, we investigate the effect of realistic extrinsic noises acting on gene deactivation in a common network motif - the positive feedback of a transcription factor on its own synthesis - under a variety of settings, i.e., distinct cellular types, distribution of proteins and properties of the external perturbations. At variance with standard models where the perturbations are Gaussian unbounded, we focus here on bounded extrinsic noises to better mimic biological reality. Our results suggest that the gene switching velocity is a key parameter to modulate the response of the network. Simulations suggest that, if the gene switching is fast and many proteins are present, an irreversible noise-induced first order transition is observed as a function of the noise intensity. If noise intensity is further increased a second order transition is also observed. When gene switching is fast, a similar scenario is observed even when few proteins are present, provided that larger cells are considered, which is mainly influenced by noise autocorrelation. On the contrary, if the gene switching is slow, no fist order transitions are observed. In the concluding remarks possible implications of the irreversible transitions for cellular differentiation are briefly discussed.