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RESEARCH ARTICLE Open Access Negative auto-regulation increases the input

Summary: RESEARCH ARTICLE Open Access
Negative auto-regulation increases the input
dynamic-range of the arabinose system of
Escherichia coli
Daniel Madar, Erez Dekel, Anat Bren and Uri Alon*
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
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,


Source: Alon, Uri - Departments of Molecular Cell Biology & Physics of Complex Systems, Weizmann Institute of Science


Collections: Biology and Medicine