title: Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.
abstract: BACKGROUND
  Gene regulation networks are made of recurring regulatory patterns, called network motifs. One of the most common network motifs is negative auto-regulation, in which a transcription factor represses its own production. Negative auto-regulation has several potential functions: it can shorten the response time (time to reach halfway to steady-state), stabilize expression against noise, and linearize the gene's input-output response curve. This latter function of negative auto-regulation, which increases the range of input signals over which downstream genes respond, has been studied by theory and synthetic gene circuits. Here we ask whether negative auto-regulation preserves this function also in the context of a natural system, where it is embedded within many additional interactions. To address this, we studied the negative auto-regulation motif in the arabinose utilization system of Escherichia coli, in which negative auto-regulation is part of a complex regulatory network.
  
  
  RESULTS
  We find that when negative auto-regulation is disrupted by placing the regulator araC under constitutive expression, the input dynamic range of the arabinose system is reduced by 10-fold. The apparent Hill coefficient of the induction curve changes from about n = 1 with negative auto-regulation, to about n = 2 when it is disrupted. We present a mathematical model that describes how negative auto-regulation can increase input dynamic-range, by coupling the transcription factor protein level to the input signal.
  
  
  CONCLUSIONS
  Here we demonstrate that the negative auto-regulation motif in the native arabinose system of Escherichia coli increases the range of arabinose signals over which the system can respond. In this way, negative auto-regulation may help to increase the input dynamic-range while maintaining the specificity of cooperative regulatory systems. This function may contribute to explaining the common occurrence of negative auto-regulation in biological systems.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Madar
authors.forename: Erez
authors.initials: E
authors.lastname: Dekel
authors.forename: Anat
authors.initials: A
authors.lastname: Bren
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D051777:AraC Transcription Factor / Q000378:metabolism; D001089:Arabinose / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D008954:Models, Biological; D009876:Operon / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051777:AraC Transcription Factor; C497371:AraC protein, E coli; D029968:Escherichia coli Proteins; D014157:Transcription Factors; D001089:Arabinose