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 fluctuations 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 self-activation 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.

Stochastic timing in gene expression for simple regulatory strategies / A. Dal Co, M. Cosentino Lagomarsino, M. Caselle, M. Osella. - In: NUCLEIC ACIDS RESEARCH. - ISSN 1362-4962. - 45:3(2017), pp. 1069-1078.

Stochastic timing in gene expression for simple regulatory strategies

M. Cosentino Lagomarsino;
2017

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 fluctuations 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 self-activation 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.
Cell Cycle; Circadian Clocks; Computer Simulation; Gene Expression Regulation; Gene Regulatory Networks; Homeostasis; Models, Genetic; Stochastic Processes; Time Factors
Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici
Settore BIO/11 - Biologia Molecolare
2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/608076
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