title: Dynamics of transcription of closely spaced promoters in Escherichia coli, one event at a time.
abstract: Many pairs of genes in Escherichia coli are driven by closely spaced promoters. We study the dynamics of expression of such pairs of genes driven by a model at the molecule and nucleotide level with delayed stochastic dynamics as a function of the binding affinity of the RNA polymerase to the promoter region, of the geometry of the promoter, of the distance between transcription start sites (TSSs) and of the repression mechanism. We find that the rate limiting steps of transcription at the TSS, the closed and open complex formations, strongly affect the kinetics of RNA production for all promoter configurations. Beyond a certain rate of transcription initiation events, we find that the interference between polymerases correlates the dynamics of production of the two RNA molecules from the two TSS and affects the distribution of intervals between consecutive productions of RNA molecules. The degree of correlation depends on the geometry, the distance between TSSs and repressors. Small changes in the distance between TSSs can cause abrupt changes in behavior patterns, suggesting that the sequence between adjacent promoters may be subject to strong selective pressure. The results provide better understanding on the sequence level mechanisms of transcription regulation in bacteria and may aid in the genetic engineering of artificial circuits based on closely spaced promoters.
authors.affiliation: Faculdade de Ciências e Tecnologia Universidade Nova de Lisboa, Monte da Caparica, 2829-516 Caparica, Portugal.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Martins
authors.forename: Jarno
authors.initials: J
authors.lastname: Mäkelä
authors.forename: Antti
authors.initials: A
authors.lastname: Häkkinen
authors.forename: Meenakshisundaram
authors.initials: M
authors.lastname: Kandhavelu
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.forename: José M
authors.initials: JM
authors.lastname: Fonseca
authors.forename: Andre S
authors.initials: AS
authors.lastname: Ribeiro
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012329:RNA, Bacterial / Q000096:biosynthesis; D013269:Stochastic Processes; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D012329:RNA, Bacterial; D012321:DNA-Directed RNA Polymerases