title: The Coordinated Positive Regulation of Topoisomerase Genes Maintains Topological Homeostasis in Streptomyces coelicolor.
abstract: Maintaining an optimal level of chromosomal supercoiling is critical for the progression of DNA replication and transcription. Moreover, changes in global supercoiling affect the expression of a large number of genes and play a fundamental role in adapting to stress. Topoisomerase I (TopA) and gyrase are key players in the regulation of bacterial chromosomal topology through their respective abilities to relax and compact DNA. Soil bacteria such as Streptomyces species, which grow as branched, multigenomic hyphae, are subject to environmental stresses that are associated with changes in chromosomal topology. The topological fluctuations modulate the transcriptional activity of a large number of genes and in Streptomyces are related to the production of antibiotics. To better understand the regulation of topological homeostasis in Streptomyces coelicolor, we investigated the interplay between the activities of the topoisomerase-encoding genes topA and gyrBA We show that the expression of both genes is supercoiling sensitive. Remarkably, increased chromosomal supercoiling induces the topA promoter but only slightly influences gyrBA transcription, while DNA relaxation affects the topA promoter only marginally but strongly activates the gyrBA operon. Moreover, we showed that exposure to elevated temperatures induces rapid relaxation, which results in changes in the levels of both topoisomerases. We therefore propose a unique mechanism of S. coelicolor chromosomal topology maintenance based on the supercoiling-dependent stimulation, rather than repression, of the transcription of both topoisomerase genes. These findings provide important insight into the maintenance of topological homeostasis in an industrially important antibiotic producer.
  
  
  
  We describe the unique regulation of genes encoding two topoisomerases, topoisomerase I (TopA) and gyrase, in a model Streptomyces species. Our studies demonstrate the coordination of topoisomerase gene regulation, which is crucial for maintenance of topological homeostasis. Streptomyces species are producers of a plethora of biologically active secondary metabolites, including antibiotics, antitumor agents, and immunosuppressants. The significant regulatory factor controlling the secondary metabolism is the global chromosomal topology. Thus, the investigation of chromosomal topology homeostasis in Streptomyces strains is crucial for their use in industrial applications as producers of secondary metabolites.
authors.affiliation: University of Wroclaw, Faculty of Biotechnology, Laboratory of Molecular Microbiology, Wroclaw, Poland marcin.szafran@uwr.edu.pl.
authors.forename: Marcin Jan
authors.initials: MJ
authors.lastname: Szafran
authors.affiliation: University of Wroclaw, Faculty of Biotechnology, Laboratory of Molecular Microbiology, Wroclaw, Poland.
authors.forename: Martyna
authors.initials: M
authors.lastname: Gongerowska
authors.affiliation: Wroclaw University of Technology, Faculty of Chemistry, Wroclaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Gutkowski
authors.affiliation: University of Wroclaw, Faculty of Biotechnology, Laboratory of Molecular Microbiology, Wroclaw, Poland Institute of Immunology and Experimental Therapy, Laboratory of Microbiology, Wroclaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Zakrzewska-Czerwińska
authors.affiliation: University of Wroclaw, Faculty of Biotechnology, Laboratory of Molecular Microbiology, Wroclaw, Poland Institute of Immunology and Experimental Therapy, Laboratory of Microbiology, Wroclaw, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Jakimowicz
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D027081:DNA Gyrase / Q000235:genetics* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D009876:Operon; D011401:Promoter Regions, Genetic; D048372:Streptomyces coelicolor / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004264:DNA Topoisomerases, Type I; D027081:DNA Gyrase