Artículo
Pervasive transcription enhances the accessibility of H-NS–silenced promoters and generates bistability in Salmonella virulence gene expression
Autor/es | Figueroa Bossi, Nara
Sánchez Romero, María Antonia Kerboriou, Patricia Naquin, Delphine Mendes, Clara Bouloc, Philippe Casadesus Pursals, Josep Bossi, Lionello |
Departamento | Universidad de Sevilla. Departamento de Microbiología y Parasitología Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2022 |
Fecha de depósito | 2023-05-30 |
Publicado en |
|
Resumen | 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 ... 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 50 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. |
Agencias financiadoras | Agence Nationale de la Recherche. France Ministerio de Ciencia e Innovación (MICIN). España Agencia Estatal de Investigación. España |
Identificador del proyecto | ANR-15-CE11-0024-03
PID2020-116995RB-I00 |
Cita | Figueroa Bossi, N., Sánchez Romero, M.A., Kerboriou, P., Naquin, D., Mendes, C., Bouloc, P.,...,Bossi, L. (2022). 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 (PNAS), 119 (30), e2203011119. https://doi.org/10.1073/pnas.2203011119. |
Ficheros | Tamaño | Formato | Ver | Descripción |
---|---|---|---|---|
pnas.2203011119.pdf | 1.797Mb | [PDF] | Ver/ | |