title: Dissecting specific and global transcriptional regulation of bacterial gene expression.
abstract: Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional--but often neglected--layer of complexity in gene expression. Here, we develop an experimental-computational approach to dissect specific and global regulation in the bacterium Escherichia coli. By using fluorescent promoter reporters, we show that global regulation is growth rate dependent not only during steady state but also during dynamic changes in growth rate and can be quantified through two promoter-specific parameters. By applying our approach to arginine biosynthesis, we obtain a quantitative understanding of both specific and global regulation that allows accurate prediction of the temporal response to simultaneous perturbations in arginine availability and growth rate. We thereby uncover two principles of joint regulation: (i) specific regulation by repression dominates the transcriptional response during metabolic steady states, largely repressing the biosynthesis genes even when biosynthesis is required and (ii) global regulation sets the maximum promoter activity that is exploited during the transition between steady states.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Gerosa
authors.forename: Karl
authors.initials: K
authors.lastname: Kochanowski
authors.forename: Matthias
authors.initials: M
authors.lastname: Heinemann
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
mesh_terms: D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D048168:Escherichia coli K12 / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007700:Kinetics; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D029968:Escherichia coli Proteins; D049452:Green Fluorescent Proteins; D001120:Arginine