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.
Highlights
Bacteria sense a wide array of signals
We study the effect of autoregulation on intracellular LacI concentration and build a stochastic model of the lactose utilization system to explore the role of LacI autoregulation
We have developed a mathematical model to study the effects of LacI autoregulation
Summary
Bacteria sense a wide array of signals (minerals, nutrients, stress signals, etc.). A large class of cellular response systems regulates the flux and concentration of small molecules by controlling transport and metabolism pathways via two feedback loops connected by a common transcription regulatory protein that senses the intracellular concentration of the small molecule [1,2]. The lacI gene is present just upstream of the lac operon, and there are three operator sites where the LacI tetramer can bind and affect transcription [5]. LacI binding to O1 represses transcription of the lac operon but leaves the expression of the lacI gene unchanged. When O1 and O3 are bound, is the lac operon repressed, but the production of LacI is prevented [9]. In this state, transcription of lacI occurs but only a truncated transcript is produced, which is in turn subject to SsrA-mediated tagging and subsequent proteolysis of the truncated protein produced [9]. While there is experimental evidence for LacI autoregulation [9,10], this feature of the network is ignored by the available mathematical
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