Analysis of the hierarchical structure of the B. subtilis transcriptional regulatory network

TL;DR

This study analyzes the hierarchical structure of Bacillus subtilis's transcriptional regulatory network, comparing it with Escherichia coli, revealing organizational principles and differences that relate to functional regulation and adaptability.

Contribution

It introduces a graph-theoretic method to categorize bacterial TRNs into hierarchical levels and compares structural and functional differences between B. subtilis and E. coli.

Findings

Hierarchical levels of transcription factors identified in both bacteria.

Differences in sigma-factor distribution explain organizational variations.

Hierarchical structure correlates with regulatory flexibility.

Abstract

The transcriptional regulation of gene expression is orchestrated by complex networks of interacting genes. Increasing evidence indicates that these transcriptional regulatory networks (TRNs) in bacteria have an inherently hierarchical architecture, although the design principles and the specific advantages offered by this type of organization have not yet been fully elucidated. In this study, we focussed on the hierarchical structure of the TRN of the gram-positive bacterium Bacillus subtilis and performed a comparative analysis with the TRN of the gram-negative bacterium Escherichia coli. Using a graph-theoretic approach, we organized the transcription factors (TFs) and sigma-factors in the TRNs of B. subtilis and E. coli into three hierarchical levels (Top, Middle and Bottom) and studied several structural and functional properties across them. In addition to many similarities, we found also specific differences, explaining the majority of them with variations in the distribution of sigma-factors across the hierarchical levels in the two organisms. We then investigated the control of target metabolic genes by transcriptional regulators to characterize the differential regulation of three distinct metabolic subsystems (catabolism, anabolism and central energy metabolism). These results suggest that the hierarchical architecture that we observed in B. subtilis represents an effective organization of its TRN to achieve flexibility in the response to diverse stimuli.