Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli

TL;DR

This study reveals how different subnet scales in E. coli's transcriptional regulatory network exhibit distinct regulatory patterns, with some subnets showing more variation influenced by both transcription factors and RNA regulation, and others being more stable with specific motifs.

Contribution

It introduces a subnet-based analysis of the E. coli TRN, linking network motifs and regulatory mechanisms to gene expression variability across environmental and genetic changes.

Findings

Subnets with less expression change have more feed-forward loops.

Subnets with more variation are regulated by both transcription factors and RNA.

Distinct regulatory scales exist within the E. coli TRN.

Abstract

The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with less changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: 1) subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation, and 2) subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.