title: Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk.
abstract: Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN.
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Eckweiler
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Agata
authors.initials: A
authors.lastname: Bielecka
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Nicolai
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Raimo
authors.initials: R
authors.lastname: Franke
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dötsch
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hornischer
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bruchmann
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Düvel
authors.affiliation: Institute for Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D059014:High-Throughput Nucleotide Sequencing; D006790:Host-Parasite Interactions / Q000502:physiology*; D011552:Pseudomonas Infections / Q000235:genetics* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D017423:Sequence Analysis, RNA; D012808:Sigma Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D059467:Transcriptome
chemical_list: D012808:Sigma Factor