Expansion of the Cra regulatory network and conservation of transcriptional regulation in carbon metabolism of Escherichia coli
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ABSTRACT:
ORGANISM(S): Escherichia coli str. K-12 substr. MG1655
PROVIDER: GSE232785 | GEO | 2025/08/11
REPOSITORIES: GEO
Similar Datasets
Project description:Carbon metabolism in diverse bacteria is primarily governed by two key transcription factors, CRP and Cra. Although numerous studies have investigated their regulatory mechanisms under glucose conditions, the understanding of their role in controlling central metabolism across different carbon sources, such as galactose, remains limited, with scarce in vivo binding information available. In this study, we focused on the Cra binding profile of Escherichia coli grown on galactose, an unfavorable carbon source. While genome-wide Cra binding sites on galactose closely resemble that on glucose, however, further examination of transcriptomic and flux simulation data suggests a complex regulatory mechanism by which Cra modulates central carbon metabolism on galactose. Additionally, conservation analysis across a wide range of bacterial taxa revealed that Cra and its regulons are more broadly conserved compared to CRP and its regulons, indicating a potential role for Cra in the early evolution of bacterial central carbon metabolism.
2025-08-11 | GSE119894 | GEO
Project description:Carbon metabolism in diverse bacteria is primarily governed by two key transcription factors, CRP and Cra. Although numerous studies have investigated their regulatory mechanisms under glucose conditions, the understanding of their role in controlling central metabolism across different carbon sources, such as galactose, remains limited, with scarce in vivo binding information available. In this study, we focused on the Cra binding profile of Escherichia coli grown on galactose, an unfavorable carbon source. While genome-wide Cra binding sites on galactose closely resemble that on glucose, however, further examination of transcriptomic and flux simulation data suggests a complex regulatory mechanism by which Cra modulates central carbon metabolism on galactose. Additionally, conservation analysis across a wide range of bacterial taxa revealed that Cra and its regulons are more broadly conserved compared to CRP and its regulons, indicating a potential role for Cra in the early evolution of bacterial central carbon metabolism.
2025-08-11 | GSE232784 | GEO
Project description:Expansion of the Cra regulatory network and conservation of transcriptional regulation in carbon metabolism of Escherichia coli
| PRJNA973954 | ENA
Project description:Gastrointestinal (GI) bacteria sense diverse environmental signals as cues for differential gene regulation and niche adaptation. Pathogens such as enterohemorrhagic Escherichia coli (EHEC), which causes bloody diarrhea, use these signals for the temporal and energy-efficient regulation of their virulence factors. One of the main virulence strategies employed by EHEC is the formation of attaching and effacing (AE) lesions on enterocytes. Most of the genes necessary for the formation of these lesions are grouped within a pathogenicity island, the locus of enterocyte effacement (LEE), whose expression requires the LEE-encoded regulator Ler. Here we show that growth of EHEC in glycolytic environments inhibits the expression of ler and consequently all other LEE genes. Conversely, growth within a gluconeogenic environment activates expression of these genes. This sugar-dependent regulation is achieved through two transcription factors: KdpE and Cra. Both Cra and KdpE directly bind to the ler promoter, and Cra's affinity to this promoter is catabolite dependent. Moreover, we show that the Cra and KdpE proteins interact in vitro and that KdpE's ability to bind DNA is enhanced by the presence of Cra. Cra is important for AE lesion formation, and KdpE contributes to this Cra-dependent regulation. The deletion of cra and kdpE resulted in the ablation of AE lesions. One of the many challenges that bacteria face within the GI tract is to successfully compete for carbon sources. Linking carbon metabolism to the precise coordination of virulence expression is a key step in the adaptation of pathogens to the GI environment. IMPORTANCE An appropriate and prompt response to environmental cues is crucial for bacterial survival. Cra and KdpE are two proteins found in both nonpathogenic and pathogenic bacteria that regulate genes in response to differences in metabolite concentration. In this work, we show that, in the deadly pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7, which causes bloody diarrhea, these two proteins influence important virulence traits. We also propose that their control of one or more of these virulence traits is due to the direct interaction of the Cra and KdpE proteins with each other, as well as with their DNA targets. This work shows how EHEC coopts established mechanisms for sensing the metabolites and stress cues in the environment, to induce virulence factors in a temporal and energy-efficient manner, culminating in disease. Understanding how pathogens commandeer nonpathogenic systems can help us develop measures to control them.
| S-EPMC3482499 | biostudies-literature
Project description:Cra (catabolite repressor activator) is a global regulator of the genes for carbon metabolism in Escherichia coli. To gain insights into the regulatory roles of Cra, attempts were made to identify the whole set of regulation targets using an improved genomic SELEX (systematic evolution of ligands by exponential enrichment) system. Surprisingly, a total of 164 binding sites were identified for Cra, 144 (88%) of which were newly identified. The majority of known targets were included in the SELEX chip pattern. The promoters examined by the lacZ reporter assay in vivo were all regulated by Cra. These two lines of evidence indicate that a total of as many as 178 promoters are under the control of Cra. The majority of Cra targets are the genes coding for the enzymes involved in central carbon metabolism, covering all the genes for the enzymes involved in glycolysis and metabolism downstream of glycolysis, including the tricarboxylic acid (TCA) cycle and aerobic respiration. Taken together, we propose that Cra plays a key role in balancing the levels of the enzymes for carbon metabolism.
| S-EPMC3021228 | biostudies-literature
Project description:Expansion of the Cra regulatory network and conservation of transcriptional regulation in carbon metabolism of Escherichia coli [RNA-seq]
| PRJNA973962 | ENA
Project description:Expansion of the Cra regulatory network and conservation of transcriptional regulation in carbon metabolism of Escherichia coli [ChIP-exo]
| PRJNA490633 | ENA
Project description:Two major transcriptional regulators of carbon metabolism in bacteria are Cra and CRP. CRP is considered to be the main mediator of catabolite repression. Unlike for CRP, in vivo DNA binding information of Cra is scarce. Here we generate and integrate ChIP-exo and RNA-seq data to identify 39 binding sites for Cra and 97 regulon genes that are regulated by Cra in Escherichia coli. An integrated metabolic-regulatory network was formed by including experimentally-derived regulatory information and a genome-scale metabolic network reconstruction. Applying analysis methods of systems biology to this integrated network showed that Cra enables optimal bacterial growth on poor carbon sources by redirecting and repressing glycolysis flux, by activating the glyoxylate shunt pathway, and by activating the respiratory pathway. In these regulatory mechanisms, the overriding regulatory activity of Cra over CRP is fundamental. Thus, elucidation of interacting transcriptional regulation of core carbon metabolism in bacteria by two key transcription factors was possible by combining genome-wide experimental measurement and simulation with a genome-scale metabolic model.
| S-EPMC5888115 | biostudies-literature
Project description:Genome-scale metabolic models have become a fundamental tool for examining metabolic principles. However, metabolism is not solely characterized by the underlying biochemical reactions and catalyzing enzymes, but also affected by regulatory events. Since the pioneering work of Covert and co-workers as well as Shlomi and co-workers it is debated, how regulation and metabolism synergistically characterize a coherent cellular state. The first approaches started from metabolic models, which were extended by the regulation of the encoding genes of the catalyzing enzymes. By now, bioinformatics databases in principle allow addressing the challenge of integrating regulation and metabolism on a system-wide level. Collecting information from several databases we provide a network representation of the integrated gene regulatory and metabolic system for Escherichia coli, including major cellular processes, from metabolic processes via protein modification to a variety of regulatory events. Besides transcriptional regulation, we also take into account regulation of translation, enzyme activities and reactions. Our network model provides novel topological characterizations of system components based on their positions in the network. We show that network characteristics suggest a representation of the integrated system as three network domains (regulatory, metabolic and interface networks) instead of two. This new three-domain representation reveals the structural centrality of components with known high functional relevance. This integrated network can serve as a platform for understanding coherent cellular states as active subnetworks and to elucidate crossover effects between metabolism and gene regulation.
| S-EPMC6519848 | biostudies-literature
Project description:A principal aim of systems biology is to develop in silico models of whole cells or cellular processes that explain and predict observable cellular phenotypes. Here, we use a model of a genome-scale reconstruction of the integrated metabolic and transcriptional regulatory networks for Escherichia coli, composed of 1,010 gene products, to assess the properties of all functional states computed in 15,580 different growth environments. The set of all functional states of the integrated network exhibits a discernable structure that can be visualized in 3-dimensional space, showing that the transcriptional regulatory network governing metabolism in E. coli responds primarily to the available electron acceptor and the presence of glucose as the carbon source. This result is consistent with recently published experimental data. The observation that a complex network composed of 1,010 genes is organized to achieve few dominant modes demonstrates the utility of the systems approach for consolidating large amounts of genome-scale molecular information about a genome and its regulation to elucidate an organism's preferred environments and functional capabilities.
| S-EPMC1323155 | biostudies-literature