The effect of LacI autoregulation on the performance of the lactose utilization system in Escherichia coli

TY - JOUR

T1 - The effect of LacI autoregulation on the performance of the lactose utilization system in Escherichia coli

AU - Semsey, Szabolcs

AU - Pedersen, Liselotte Jauffred

AU - Csiszovszki, Z.

AU - Erdossy, J.

AU - Steger, V.

AU - Hansen, Sabine

AU - Krishna, Sandeep

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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 cAMPCRP 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.

AB - 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 cAMPCRP 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.

U2 - 10.1093/nar/gkt351

DO - 10.1093/nar/gkt351

M3 - Journal article

C2 - 23658223

SN - 0305-1048

VL - 41

SP - 6381

EP - 6390

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 13

ER -