Widespread suppression of intragenic transcription initiation by H-NS

Singh, Shivani; Singh, Navjot; Bonocora, Richard P.; Fitzgerald, Devon M.; Wade, Joseph T.; Grainger, David C.

doi:10.1101/gad.234336.113

Cited by 153 publications

(182 citation statements)

References 37 publications

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“…Internal binding of transcriptional regulators within a gene in bacteria has been seen in many instances, and recently, it has also been observed for flhDC and fliA (83)(84)(85)(86)(87). In this particular case of MrpJflhDC regulation, these intragenic signals could originate from additional MrpJ-DNA interactions, or alternatively, they could arise from a condensed higher-order conformation of the P. mirabilis chromosome in this region (67)(68)(69)(70)88).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

et al. 2015

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The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence. Bacterial pathogens utilize a myriad of complex regulatory networks to adapt gene expression in response to environmental cues encountered in the host. Trying to walk a fine balance of avoiding detection by the host immune system, while ensuring acquisition of all essential nutrients and promoting growth, bacteria employ transcriptional and posttranscriptional strategies to combat the host's defenses. A prominent example is the specific induction of iron and zinc uptake systems during infection, regulated by Fur and Zur, respectively, which allows pathogens to gain access to these essential transition metals in the restricted host environment (1, 2).Urinary tract infections (UTIs) are among the most common bacterial infections (3), presenting a significant public health burden amounting to annual costs of about 3.5 billion dollars in the United States alone (4). Although Proteus mirabilis causes a relatively small proportion of UTIs in healthy individuals, it is a common cause of cystitis and pyelonephritis in individuals with indwelling catheters or anatomical abnormalities of the urinary tract (4, 5).UTIs occur almost exclusively in an ascending route, meaning that bacteria of fecal origin gain entry to the bladder via the urethra and then spread to the kidneys via the ureters (4). Initially, bacteria adhere to host epithelial cells via proteinaceous supramolecular structures referred to as fimbriae (or pili) (6), which allow pathogens to withstand the mechanical flow of urine (5)...

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Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

et al. 2015

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“…E. coli strain RPB104 (MG1655 with C-terminally SPA-tagged rpoS) was grown overnight in M9 minimal medium with 0.4% glycerol at 30°C, then subcultured 1:100 in the same medium, and grown for 60 h to saturation (optical density at 600 nm of ϳ3). ChIP-seq using the M2 monoclonal anti-FLAG antibody was performed as described previously (80). Regions of enrichment (peaks) were identified as described previously (23).…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Transcriptional Response to Varying RpoS Levels in Escherichia coli K-12

et al. 2017

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The alternative sigma factor RpoS is a central regulator of many stress responses in Escherichia coli. The level of functional RpoS differs depending on the stress. The effect of these differing concentrations of RpoS on global transcriptional responses remains unclear. We investigated the effect of RpoS concentration on the transcriptome during stationary phase in rich media. We found that 23% of genes in the E. coli genome are regulated by RpoS, and we identified many RpoS-transcribed genes and promoters. We observed three distinct classes of response to RpoS by genes in the regulon: genes whose expression changes linearly with increasing RpoS level, genes whose expression changes dramatically with the production of only a little RpoS ("sensitive" genes), and genes whose expression changes very little with the production of a little RpoS ("insensitive"). We show that sequences outside the core promoter region determine whether an RpoS-regulated gene is sensitive or insensitive. Moreover, we show that sensitive and insensitive genes are enriched for specific functional classes and that the sensitivity of a gene to RpoS corresponds to the timing of induction as cells enter stationary phase. Thus, promoter sensitivity to RpoS is a mechanism to coordinate specific cellular processes with growth phase and may also contribute to the diversity of stress responses directed by RpoS. IMPORTANCEThe sigma factor RpoS is a global regulator that controls the response to many stresses in Escherichia coli. Different stresses result in different levels of RpoS production, but the consequences of this variation are unknown. We describe how changing the level of RpoS does not influence all RpoS-regulated genes equally. The cause of this variation is likely the action of transcription factors that bind the promoters of the genes. We show that the sensitivity of a gene to RpoS levels explains the timing of expression as cells enter stationary phase and that genes with different RpoS sensitivities are enriched for specific functional groups. Thus, promoter sensitivity to RpoS is a mechanism that coordinates specific cellular processes in response to stresses. KEYWORDS RpoS, promoters, S , stress response, transcriptional regulation, transcriptome G enome-wide measurements of RNA levels have revolutionized our understanding of how cells organize their patterns of transcription. These studies have given us snapshots of how patterns of gene expression change in response to changes in the external environment. They have also allowed us to define the regulons controlled by specific transcription factors (TFs). A major weakness of the vast majority of these

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“…11,12 Nevertheless, the average intensity of selection against such elements is weak, and, consequently, many spurious promoterlike sequences persist within populations. 13 Because uncontrolled transcription from genome-wide promoter-like sequences are potentially dangerous, bacteria have several systems in place to control the generation of spurious transcripts: (i) The histone-like nucleoid structuring protein (H-NS) suppresses transcription initiation from intragenic promoters, 14 (ii) the termination factor Rho and its cofactor NusG function in the termination of asRNA transcription, 15,16 and (iii) multiple RNases degrade aberrant RNAs. 17 A lack of asRNA conservation among closely related bacteria might not necessarily indicate lack of function because, as shown recently in Drosophila, functional genes can arise rapidly in a lineage-specific manner.…”

Section: Introductionmentioning

confidence: 99%