Genome-wide gene expression noise in Escherichia coli is condition-dependent and determined by propagation of noise through the regulatory network.

Arantxa Urchueguía,Luca Galbusera,Thomas Julou,Dany Chauvin,Erik Van Nimwegen,Gwendoline Bellement,Nathalie Balaban

doi:10.1371/journal.pbio.3001491

Arantxa Urchueguía, Luca Galbusera + Show 5 more

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https://doi.org/10.1371/journal.pbio.3001491

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Abstract

Although it is well appreciated that gene expression is inherently noisy and that transcriptional noise is encoded in a promoter's sequence, little is known about the extent to which noise levels of individual promoters vary across growth conditions. Using flow cytometry, we here quantify transcriptional noise in Escherichia coli genome-wide across 8 growth conditions and find that noise levels systematically decrease with growth rate, with a condition-dependent lower bound on noise. Whereas constitutive promoters consistently exhibit low noise in all conditions, regulated promoters are both more noisy on average and more variable in noise across conditions. Moreover, individual promoters show highly distinct variation in noise across conditions. We show that a simple model of noise propagation from regulators to their targets can explain a significant fraction of the variation in relative noise levels and identifies TFs that most contribute to both condition-specific and condition-independent noise propagation. In addition, analysis of the genome-wide correlation structure of various gene properties shows that gene regulation, expression noise, and noise plasticity are all positively correlated genome-wide and vary independently of variations in absolute expression, codon bias, and evolutionary rate. Together, our results show that while absolute expression noise tends to decrease with growth rate, relative noise levels of genes are highly condition-dependent and determined by the propagation of noise through the gene regulatory network.

Highlights

It is well established that isogenic cells growing in a homogeneous environment show cell-to-cell fluctuations in gene expression
Using methodology already employed in several previous studies [7,9,20], we used flow cytometry together with a library of fluorescent transcriptional reporters [21] to measure gene expression distributions of E. coli promoters genome-wide across a set of 8 different growth conditions (Fig 1A)
We propose that the qualitative patterns in Condition-dependent gene expression noise in E. coli is determined by noise propagation expression noise across conditions that we observed in Fig 2 and Fig K in S1 Text can be explained by assuming that noise levels are to a large extent determined by propagation of noise from regulators to their targets

Summary

Introduction

It is well established that isogenic cells growing in a homogeneous environment show cell-to-cell fluctuations in gene expression (for example, [1,2,3,4]). This gene expression noise is not surprising from a biophysical perspective, given the inherent thermodynamic fluctuations in the molecular events underlying gene expression and the small numbers of molecules involved.

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