title: The effect of LacI autoregulation on the performance of the lactose utilization system in Escherichia coli.
abstract: The lactose operon of Escherichia coli is a paradigm system for quantitative understanding of gene regulation in prokaryotes. Yet, none of the many mathematical models built so far to study the dynamics of this system considered the fact that the Lac repressor regulates its own transcription by forming a transcriptional roadblock at the O3 operator site. Here we study the effect of autoregulation on intracellular LacI levels and also show that cAMP-CRP binding does not affect the efficiency of autoregulation. We built a mathematical model to study the role of LacI autoregulation in the lactose utilization system. Previously, it has been argued that negative autoregulation can significantly reduce noise as well as increase the speed of response. We show that the particular molecular mechanism, a transcriptional roadblock, used to achieve self-repression in the lac system does neither. Instead, LacI autoregulation balances two opposing states, one that allows quicker response to smaller pulses of external lactose, and the other that minimizes production costs in the absence of lactose.
authors: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark. semsey@nbi.dk
authors: Szabolcs
authors: S
authors: Semsey
authors: Liselotte
authors: L
authors: Jauffred
authors: Zsolt
authors: Z
authors: Csiszovszki
authors: János
authors: J
authors: Erdossy
authors: Viktor
authors: V
authors: Stéger
authors: Sabine
authors: S
authors: Hansen
authors: Sandeep
authors: S
authors: Krishna
mesh_terms: D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D007763:Lac Operon; D056968:Lac Repressors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007785:Lactose / Q000378:metabolism*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D012333:RNA, Messenger; D007785:Lactose
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