Kinetic Modeling and Meta-Analysis of the Bacillus subtilis SigB Regulon during Spore Germination and Outgrowth.

Jiri Vohradsky,Viola Vaňková Hausnerová,Olga Ramaniuk,Marek Schwarz,Libor Krásný,Hana Šanderová,Olatz Ruiz-Larrabeiti

doi:10.3390/microorganisms9010112

Jiri Vohradsky, Viola Vaňková Hausnerová + Show 5 more

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https://doi.org/10.3390/microorganisms9010112

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Abstract

The exponential increase in the number of conducted studies combined with the development of sequencing methods have led to an enormous accumulation of partially processed experimental data in the past two decades. Here, we present an approach using literature-mined data complemented with gene expression kinetic modeling and promoter sequence analysis. This approach allowed us to identify the regulon of Bacillus subtilis sigma factor SigB of RNA polymerase (RNAP) specifically expressed during germination and outgrowth. SigB is critical for the cell’s response to general stress but is also expressed during spore germination and outgrowth, and this specific regulon is not known. This approach allowed us to (i) define a subset of the known SigB regulon controlled by SigB specifically during spore germination and outgrowth, (ii) identify the influence of the promoter sequence binding motif organization on the expression of the SigB-regulated genes, and (iii) suggest additional sigma factors co-controlling other SigB-dependent genes. Experiments then validated promoter sequence characteristics necessary for direct RNAP–SigB binding. In summary, this work documents the potential of computational approaches to unravel new information even for a well-studied system; moreover, the study specifically identifies the subset of the SigB regulon, which is activated during germination and outgrowth.

Highlights

Transcription and expression of the physiologically relevant genes is essential for adaptation of organisms to changing environmental conditions
In this study, using a combined approach of static and dynamic information analyses, we defined the SigB regulon in B. subtilis that is active during spore germination and outgrowth
The used approach combined a meta-analysis of literature data with the information about the kinetics of gene expression and promoter sequence analysis

Summary

Introduction

Transcription and expression of the physiologically relevant genes is essential for adaptation of organisms to changing environmental conditions. Uncovering the nature of gene regulatory networks is one of the core tasks of systems biology. A number of tools for gene regulatory network inference were developed in the last 20 years (a comprehensive review of the methods for gene networks inference can be found in Wang et al [2] and Loskot et al [3]). Several such tools (ARACNE [4], and network BMA [5]), including our tool CyGenexpi [6], were integrated into the systems biology platform Cytoscape (http://www.cytoscape.org/).

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