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dc.contributor.authorRodrigo, Guillermoes_ES
dc.contributor.authorBajic, Djordjees_ES
dc.contributor.authorElola, Ignacioes_ES
dc.contributor.authorPoyatos, Juan F.es_ES
dc.identifier.citationScientific Reportses_ES
dc.description.abstractBy integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.es_ES
dc.description.sponsorshipThis work was partially funded by grants GV/2016/079 (GVA) and BFU2011-24691 (MINECO). We thank T. Miyashiro and M. Goulian for strains, T. Cordero and J. Rodriguez-Beltran for technical assistance, and J.L. Rosner and R.G. Martin for discussions on earlier studies on the mar system. We also thank L.D. Hurst for comments on a previous draft.es_ES
dc.titleAntagonistic autoregulation speeds up a homogeneous response in Escherichia colies_ES
dc.description.peerreviewedPeer reviewedes_ES
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