Stochastic timing in gene expression for simple regulatory strategies

Abstract

Timing is essential for many cellular processes, from cellular responses to external stimuli to the cell cycle and circadian clocks. Many of these processes are based on gene expression. For example, an activated gene may be required to reach in a precise time a threshold level of expression that triggers a specific downstream process. However, gene expression is subject to stochastic fluctuations, naturally inducing an uncertainty in this threshold-crossing time with potential consequences on biological functions and phenotypes. Here, we consider such "timing fluctuations", and we ask how they can be controlled. Our analytical estimates and simulations show that, for an induced gene, timing variability is minimal if the threshold level of expression is approximately half of the steady-state level. Timing fuctuations can be reduced by increasing the transcription rate, while they are insensitive to the translation rate. In presence of self-regulatory strategies, we show that self-repression reduces timing noise for threshold levels that have to be reached quickly, while selfactivation is optimal at long times. These results lay a framework for understanding stochasticity of endogenous systems such as the cell cycle, as well as for the design of synthetic trigger circuits.

arXiv comment10 pages, 5 figures

References in corpus (8)

• Analytical distributions for stochastic gene expression
• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Colored extrinsic fluctuations and stochastic gene expression
• Determining the stability of genetic switches: explicitly accounting for mRNA noise
• Absolute Rate Theories of Epigenetic Stability
• Hierarchy and Feedback in the Evolution of the E. coli Transcription Network
• DnaA and the timing of chromosome replication in Escherichia coli as a function of growth rate
• Growth-rate-dependent dynamics of a bacterial genetic oscillator

Cited by in corpus (4)

• Temporal precision of regulated gene expression
• Thermodynamic uncertainty relation to assess biological processes
• Escape dynamics of a self-propelled nanorod from circular confinements with narrow openings
• Role of activity and dissipation in achieving precise beating in cilia: Insights from the rower model