title: The genome-scale interplay amongst xenogene silencing, stress response and chromosome architecture in Escherichia coli.
abstract: The gene expression state of exponentially growing Escherichia coli cells is manifested by high expression of essential and growth-associated genes and low levels of stress-related and horizontally acquired genes. An important player in maintaining this homeostasis is the H-NS-StpA gene silencing system. A Δhns-stpA deletion mutant results in high expression of otherwise-silent horizontally acquired genes, many located in the terminus-half of the chromosome, and an indirect downregulation of many highly expressed genes. The Δhns-stpA double mutant displays slow growth. Using laboratory evolution we address the evolutionary strategies that E. coli would adopt to redress this gene expression imbalance. We show that two global gene regulatory mutations-(i) point mutations inactivating the stress-responsive sigma factor RpoS or σ38 and (ii) an amplification of ∼40% of the chromosome centred around the origin of replication-converge in partially reversing the global gene expression imbalance caused by Δhns-stpA. Transcriptome data of these mutants further show a three-way link amongst the global gene regulatory networks of H-NS and σ38, as well as chromosome architecture. Increasing gene expression around the terminus of replication results in a decrease in the expression of genes around the origin and vice versa; this appears to be a persistent phenomenon observed as an association across ∼300 publicly-available gene expression data sets for E. coli. These global suppressor effects are transient and rapidly give way to more specific mutations, whose roles in reversing the growth defect of H-NS mutations remain to be understood.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore 560065, India Manipal University, Manipal 576104, India.
authors.forename: Rajalakshmi
authors.initials: R
authors.lastname: Srinivasan
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore 560065, India Manipal University, Manipal 576104, India Genomic Physics Group, UMR 7238 CNRS Microorganism Genomics, UPMC, Paris, France.
authors.forename: Vittore Ferdinando
authors.initials: VF
authors.lastname: Scolari
authors.affiliation: Genomic Physics Group, UMR 7238 CNRS Microorganism Genomics, UPMC, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR 7238, Computational and Quantitative Biology, 15 Rue de l'École de Médecine Paris, France CNRS, UMR 7238, Paris, France.
authors.forename: Marco Cosentino
authors.initials: MC
authors.lastname: Lagomarsino
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore 560065, India aswin@ncbs.res.in.
authors.forename: Aswin Sai Narain
authors.initials: AS
authors.lastname: Seshasayee
mesh_terms: D002876:Chromosomes, Bacterial; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D019020:Directed Molecular Evolution; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D016680:Genome, Bacterial; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D012808:Sigma Factor; C090104:StpA protein, E coli; C116822:hns protein, E coli; C106402:RNA polymerase Esigma(38); D012321:DNA-Directed RNA Polymerases