Abstract

BackgroundQuantitative analysis of simple molecular networks is an important step forward understanding fundamental intracellular processes. As network motifs occurring recurrently in complex biological networks, gene auto-regulatory circuits have been extensively studied but gene expression dynamics remain to be fully understood, e.g., how promoter leakage affects expression noise is unclear.ResultsIn this work, we analyze a gene model with auto regulation, where the promoter is assumed to have one active state with highly efficient transcription and one inactive state with very lowly efficient transcription (termed as promoter leakage). We first derive the analytical distribution of gene product, and then analyze effects of promoter leakage on expression dynamics including bursting kinetics. Interestingly, we find that promoter leakage always reduces expression noise and that increasing the leakage rate tends to simplify phenotypes. In addition, higher leakage results in fewer bursts.ConclusionsOur results reveal the essential role of promoter leakage in controlling expression dynamics and further phenotype. Specifically, promoter leakage is a universal mechanism of reducing expression noise, controlling phenotypes in different environments and making the gene produce generate fewer bursts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0157-z) contains supplementary material, which is available to authorized users.

Highlights

  • Quantitative analysis of simple molecular networks is an important step forward understanding fundamental intracellular processes

  • A question naturally arises: in the case of feedback loop, how does promoter leakage impact expression noise? By analyzing effects of promoter leakage on gene expression using the above-mentioned three gene models, we find that promoter leakage always reduces expression noise, regardless of models, feedback types and model parameters as well as whether or not the expression level is fixed

  • This implies an important fact that promoter leakage is a universal mechanism of reducing expression noise

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Summary

Introduction

Quantitative analysis of simple molecular networks is an important step forward understanding fundamental intracellular processes. Gene expression dynamics is a lasting issue in Systems Biology and has attracted extensive attention. Quantifying the contributions of different sources of noise using stochastic models of gene expression is an important step towards understanding fundamental cellular processes and cellto-cell variability. Many theoretical models of gene expression have been proposed and become more and more subtle, from the initial one-state model [1,2] to the common two-state model [3] to those considering many detailed processes or factors, Huang et al BMC Systems Biology (2015) 9:16 noise in gene product, probability distribution, and bursting kinetics (characterized by burst size and burst frequency).

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