Extensive cross-talk and global regulators identified from an analysis of the integrated transcriptional and signaling network in Escherichia coli

Abstract

To understand the regulatory dynamics of transcription factors (TFs) and their interplay with other cellular components we have integrated transcriptional, protein-protein and the allosteric or equivalent interactions which mediate the physiological activity of TFs in Escherichia coli. To study this integrated network we computed a set of network measurements followed by principal component analysis (PCA), investigated the correlations between network structure and dynamics, and carried out a procedure for motif detection. In particular, we show that outliers identified in the integrated network based on their network properties correspond to previously characterized global transcriptional regulators. Furthermore, outliers are highly and widely expressed across conditions, thus supporting their global nature in controlling many genes in the cell. Motifs revealed that TFs not only interact physically with each other but also obtain feedback from signals delivered by signaling proteins supporting the extensive cross-talk between different types of networks. Our analysis can lead to the development of a general framework for detecting and understanding global regulatory factors in regulatory networks and reinforces the importance of integrating multiple types of interactions in underpinning the interrelationships between them.

Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes

“…Specifically, networks provide the cell with the capacity to store information within the network, outside the genome (Bhalla and Iyengar, 1999; Helikar et al, 2008), cluster standardized signaling output responses in the presence of high levels of background noise (Bhalla and Iyengar, 1999; Fritsche-Guenther et al, 2011; Helikar et al, 2008; Levy and Siegal, 2012), provide robustness to fate decisions and responsiveness to environmental change (Ku et al, 2012; Levy and Siegal, 2012), among other advantages (Bhalla et al, 2002). Given that signaling network crosstalk has been described in organisms from E. coli (Antiqueira et al, 2012) through metazoans (Natarajan et al, 2006) and humans (Ku et al, 2012), it seems clear that evolution has chosen complex, highly integrated networks as the preferred mode of intracellular information transfer (Kulkarni, 2013). …”

The Balance Metabolism Safety Net: Integration of Stress Signals by Interacting Transcriptional Factors in Streptomyces and Related Actinobacteria

“…For example, in E. coli there are only seven alternative sigma factors. The mechanism of control of the Pho regulon in E. coli is somehow different from that observed in Streptomyces species (Hsieh and Wanner, 2010;Antiqueira et al, 2012). In contrast to the strict dependence on the sensor histidine kinase PhoR in S. coelicolor (Fernández-Martínez et al, 2012), in E. coli the phosphorylation of the response regulator PhoB occurs also by acetyl-phosphate.…”

Abasy Atlas v2.2: The most comprehensive and up-to-date inventory of meta-curated, historical, bacterial regulatory networks, their completeness and system-level characterization

“…While most proteins regulate gene transcription as homodimeric complexes, the regulation of gene expression can also be achieved by heteromeric complexes, whose subunits are encoded by different genes. Despite previous integrative approaches merging different level components [25][26][27], heterodimeric complexes have not been properly represented in most of them nor databases. One of the most common representations is to assign the regulations to each subunit, leading to a duplicated representation of the interaction in the GRNs.…”