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Evolutionary expansion of a regulatory network by counter-silencing.

Will WR, Bale DH, Reid PJ, Libby SJ, Fang FC - Nat Commun (2014)

Bottom Line: Conserved genes are regulated by classical PhoP-mediated activation and are invariant in promoter architecture, whereas horizontally acquired genes exhibit variable promoter architecture and are regulated by PhoP-mediated counter-silencing.Biochemical analyses show that a horizontally acquired promoter adopts different structures in the silenced and counter-silenced states, implicating the remodelling of the H-NS nucleoprotein filament and the subsequent restoration of open-complex formation as the central mechanism of counter-silencing.Our results indicate that counter-silencing is favoured in the regulatory integration of newly acquired genes because it is able to accommodate multiple promoter architectures.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.

ABSTRACT
Horizontal gene transfer plays a major role in bacterial evolution. Successful acquisition of new genes requires their incorporation into existing regulatory networks. This study compares the regulation of conserved genes in the PhoPQ regulon of Salmonella enterica serovar Typhimurium with that of PhoPQ-regulated horizontally acquired genes, which are silenced by the histone-like protein H-NS. We demonstrate that PhoP upregulates conserved and horizontally acquired genes by distinct mechanisms. Conserved genes are regulated by classical PhoP-mediated activation and are invariant in promoter architecture, whereas horizontally acquired genes exhibit variable promoter architecture and are regulated by PhoP-mediated counter-silencing. Biochemical analyses show that a horizontally acquired promoter adopts different structures in the silenced and counter-silenced states, implicating the remodelling of the H-NS nucleoprotein filament and the subsequent restoration of open-complex formation as the central mechanism of counter-silencing. Our results indicate that counter-silencing is favoured in the regulatory integration of newly acquired genes because it is able to accommodate multiple promoter architectures.

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Genetic analysis of PhoP-regulated circuits(a) PhoP is activated via phosphorylation by the membrane-associated sensor-kinase, PhoQ, in response to low extracellular Mg2+ or cationic antimicrobial peptides at acidic pH. Phosphorylated PhoP (PhoP P) up-regulates phoP and pagC. Up-regulation of pagC also requires SlyA and repression by H NS. RT-PCR analysis of pagC (b) and phoP (c) mRNA under inducing (10 μM Mg2+) and non-inducing (10 mM Mg2+) conditions. Data represent the mean ± SEM; n = 3. Other PhoP regulon members gave similar results (Supplementary Fig. S1).
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Figure 1: Genetic analysis of PhoP-regulated circuits(a) PhoP is activated via phosphorylation by the membrane-associated sensor-kinase, PhoQ, in response to low extracellular Mg2+ or cationic antimicrobial peptides at acidic pH. Phosphorylated PhoP (PhoP P) up-regulates phoP and pagC. Up-regulation of pagC also requires SlyA and repression by H NS. RT-PCR analysis of pagC (b) and phoP (c) mRNA under inducing (10 μM Mg2+) and non-inducing (10 mM Mg2+) conditions. Data represent the mean ± SEM; n = 3. Other PhoP regulon members gave similar results (Supplementary Fig. S1).

Mentions: In this study, we use the model PhoPQ two-component signal transduction system in S. Typhimurium to examine the distinction between activation and counter-silencing. The OmpR-family transcriptional activator PhoP is essential for Salmonella virulence17,18 and exemplifies a regulatory protein capable of acting at a variety of promoter architectures19. Phosphorylation by the sensor kinase PhoQ in response to low extracellular Mg2+ concentrations or antimicrobial peptides at acidic pH20,21 allows PhoP to bind to specific promoters, resulting in transcriptional up-regulation (Fig. 1a). PhoP is able to up-regulate both horizontally-acquired and core genes possessing a wide variety of promoter architectures, but the mechanistic details of PhoP actions at different types of promoter are poorly understood. Previous studies have failed to identify any distinction between counter-silencing and activation by PhoP, and some investigators have suggested that PhoP is able to activate transcription at multiple target architectures19,22,23.


Evolutionary expansion of a regulatory network by counter-silencing.

Will WR, Bale DH, Reid PJ, Libby SJ, Fang FC - Nat Commun (2014)

Genetic analysis of PhoP-regulated circuits(a) PhoP is activated via phosphorylation by the membrane-associated sensor-kinase, PhoQ, in response to low extracellular Mg2+ or cationic antimicrobial peptides at acidic pH. Phosphorylated PhoP (PhoP P) up-regulates phoP and pagC. Up-regulation of pagC also requires SlyA and repression by H NS. RT-PCR analysis of pagC (b) and phoP (c) mRNA under inducing (10 μM Mg2+) and non-inducing (10 mM Mg2+) conditions. Data represent the mean ± SEM; n = 3. Other PhoP regulon members gave similar results (Supplementary Fig. S1).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4215172&req=5

Figure 1: Genetic analysis of PhoP-regulated circuits(a) PhoP is activated via phosphorylation by the membrane-associated sensor-kinase, PhoQ, in response to low extracellular Mg2+ or cationic antimicrobial peptides at acidic pH. Phosphorylated PhoP (PhoP P) up-regulates phoP and pagC. Up-regulation of pagC also requires SlyA and repression by H NS. RT-PCR analysis of pagC (b) and phoP (c) mRNA under inducing (10 μM Mg2+) and non-inducing (10 mM Mg2+) conditions. Data represent the mean ± SEM; n = 3. Other PhoP regulon members gave similar results (Supplementary Fig. S1).
Mentions: In this study, we use the model PhoPQ two-component signal transduction system in S. Typhimurium to examine the distinction between activation and counter-silencing. The OmpR-family transcriptional activator PhoP is essential for Salmonella virulence17,18 and exemplifies a regulatory protein capable of acting at a variety of promoter architectures19. Phosphorylation by the sensor kinase PhoQ in response to low extracellular Mg2+ concentrations or antimicrobial peptides at acidic pH20,21 allows PhoP to bind to specific promoters, resulting in transcriptional up-regulation (Fig. 1a). PhoP is able to up-regulate both horizontally-acquired and core genes possessing a wide variety of promoter architectures, but the mechanistic details of PhoP actions at different types of promoter are poorly understood. Previous studies have failed to identify any distinction between counter-silencing and activation by PhoP, and some investigators have suggested that PhoP is able to activate transcription at multiple target architectures19,22,23.

Bottom Line: Conserved genes are regulated by classical PhoP-mediated activation and are invariant in promoter architecture, whereas horizontally acquired genes exhibit variable promoter architecture and are regulated by PhoP-mediated counter-silencing.Biochemical analyses show that a horizontally acquired promoter adopts different structures in the silenced and counter-silenced states, implicating the remodelling of the H-NS nucleoprotein filament and the subsequent restoration of open-complex formation as the central mechanism of counter-silencing.Our results indicate that counter-silencing is favoured in the regulatory integration of newly acquired genes because it is able to accommodate multiple promoter architectures.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.

ABSTRACT
Horizontal gene transfer plays a major role in bacterial evolution. Successful acquisition of new genes requires their incorporation into existing regulatory networks. This study compares the regulation of conserved genes in the PhoPQ regulon of Salmonella enterica serovar Typhimurium with that of PhoPQ-regulated horizontally acquired genes, which are silenced by the histone-like protein H-NS. We demonstrate that PhoP upregulates conserved and horizontally acquired genes by distinct mechanisms. Conserved genes are regulated by classical PhoP-mediated activation and are invariant in promoter architecture, whereas horizontally acquired genes exhibit variable promoter architecture and are regulated by PhoP-mediated counter-silencing. Biochemical analyses show that a horizontally acquired promoter adopts different structures in the silenced and counter-silenced states, implicating the remodelling of the H-NS nucleoprotein filament and the subsequent restoration of open-complex formation as the central mechanism of counter-silencing. Our results indicate that counter-silencing is favoured in the regulatory integration of newly acquired genes because it is able to accommodate multiple promoter architectures.

Show MeSH
Related in: MedlinePlus