Pervasive transcription enhances the accessibility of H-NS–silenced promoters and generates bistability in $Salmonella$ virulence gene expression - I2BC Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2022

Pervasive transcription enhances the accessibility of H-NS–silenced promoters and generates bistability in $Salmonella$ virulence gene expression

Résumé

In Escherichia coli and Salmonella, many genes silenced by the nucleoid structuring protein H-NS are activated upon inhibiting Rho-dependent transcription termination. This response is poorly understood and difficult to reconcile with the view that H-NS acts mainly by blocking transcription initiation. Here we have analyzed the basis for the up-regulation of H-NS–silenced Salmonella pathogenicity island 1 (SPI-1) in cells depleted of Rho-cofactor NusG. Evidence from genetic experiments, semiquantitative 5′ rapid amplification of complementary DNA ends sequencing (5' RACE-Seq), and chromatin immunoprecipitation sequencing (ChIP-Seq) shows that transcription originating from spurious antisense promoters, when not stopped by Rho, elongates into a H-NS–bound regulatory region of SPI-1, displacing H-NS and rendering the DNA accessible to the master regulator HilD. In turn, HilD’s ability to activate its own transcription triggers a positive feedback loop that results in transcriptional activation of the entire SPI-1. Significantly, single-cell analyses revealed that this mechanism is largely responsible for the coexistence of two subpopulations of cells that either express or do not express SPI-1 genes. We propose that cell-to-cell differences produced by stochastic spurious transcription, combined with feedback loops that perpetuate the activated state, can generate bimodal gene expression patterns in bacterial populations.

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Bactériologie
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Dates et versions

hal-03826124 , version 1 (14-11-2022)

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Nara Figueroa-Bossi, María Antonia Sánchez-Romero, Patricia Kerboriou, Delphine Naquin, Clara Mendes, et al.. Pervasive transcription enhances the accessibility of H-NS–silenced promoters and generates bistability in $Salmonella$ virulence gene expression. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119, pp.e2203011119. ⟨10.1073/pnas.2203011119⟩. ⟨hal-03826124⟩
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