Escherichia coli segments its controls on carbon‐dependent gene expression into global and specific regulations

Abstract

How bacteria adjust gene expression to cope with variable environments remains open to question. Here, we investigated the way global gene expression changes in E. coli correlated with the metabolism of seven carbon substrates chosen to trigger a large panel of metabolic pathways. Coarse-grained analysis of gene co-expression identified a novel regulation pattern: we established that the gene expression trend following immediately the reduction of growth rate (GR) was correlated to its initial expression level. Subsequent fine-grained analysis of co-expression demonstrated that the Crp regulator, coupled with a change in GR, governed the response of most GR-dependent genes. By contrast, the Cra, Mlc and Fur regulators governed the expression of genes responding to non-glycolytic substrates, glycolytic substrates or phosphotransferase system transported sugars following an idiosyncratic way. This work allowed us to expand additional genes in the panel of gene complement regulated by each regulator and to elucidate the regulatory functions of each regulator comprehensively. Interestingly, the bulk of genes controlled by Cra and Mlc were, respectively, co-regulated by Crp-or GR-related effect and our quantitative analysis showed that each factor took turns to work as the primary one or contributed equally depending on the conditions.

Revisiting Fur Regulon Leads to a Comprehensive Understanding of Iron and Fur Regulation

“…However, consistent with previous findings [3], many of the downstream genes controlled by these Fur-bound promoters did not respond to Fur. Given the fact that many promoters are under coordinated control of various regulators [25,41], it was very possible that the regulations of Fur could be hampered by other regulators, and Fur regulation would emerge in some specific conditions. As a result, these promoters bound by Fur could control putative Fur regulon genes, and we will not be surprised if more Fur regulon genes are validated in the future.…”

“…However, it is obscure whether Fur is the sole regulatory factor responding to iron or not. To answer this question, we studied the transcriptomes of the Fur wild-type and knockout strains grown in minimal medium with or without supplementation of iron via high-resolution RNAseq, which we had applied to extend the regulons of several global regulators including Crp and Cra [24,25]. As listed in Figure 1A, four pairs of transcriptome comparisons could be performed.…”

Small RNA GcvB Regulates Oxidative Stress Response of Escherichia coli

“…GcvB-dependent regulation on its known targets in glucose minimal medium was almost undetectable using a traditional method [ 15 ], possibly because of the low expression of GcvB in this medium when being compared to its expression in rich medium [ 21 ]. In contrast, here, we characterized novel targets putatively controlled by GcvB in the minimal medium by applying the high-resolution RNA-seq assay that had helped us to successfully expand the members in the regulons of several global regulators [ 36 , 37 ]. Note that we also did not find the reported targets of GcvB in this medium, which is inconsistent with previous results.…”

“…Therefore, there is diversity underlining both of the physiological roles and the molecular mechanisms of GcvB, which is worthy of further extensive exploration. Since people were unable to identify the GcvB-dependent regulation in minimal medium using traditional methods as promoter- lacZ fusions [ 15 , 20 , 21 , 23 ], possibly owing to the low expression of GcvB [ 21 ], in the present work, by applying the high resolution RNA-seq assay [ 35 ] that enabled us to largely expand the members in the regulons of several global regulators [ 36 , 37 ], we identified several novel targets putatively responding to GcvB in an E. coli K-12 strain grown in minimal medium. The subsequent molecular and physiological studies enabled us to discover that GcvB controlled the oxidative stress response of E. coli via the up-regulation of OxyR, the master regulator of antioxidant genes [ 38 , 39 ].…”

A systems biology approach to disentangle the direct and indirect effects of global transcription factors on gene expression in Escherichia coli

“…While the functions and the pleiotropic effects of the global TFs are well appreciated, the true direct targets and indirect effects on gene expression together with their underlying basis for a particular environment remain unclear. These genome-wide indirect effects are primarily mediated by alterations in growth rates or physiological state of the organism that encompass regulation by RNA polymerase associated sigma factors, ribosomes, intracellular metabolites as well as by other interacting global or local TFs (Berthoumieux et al, 2013; Gerosa et al, 2013; Klumpp et al, 2009; Li et al, 2019; Pal et al, 2022; Pan et al, 2021; Utrilla et al, 2016; Yu et al, 2021). For example, the growth rate was found to exert a significant effect on the gene expression patterns in a strain lacking the global regulator CRP (Pal et al, 2022).…”