Dataset Information

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.

SUBMITTER: Madar D

PROVIDER: S-EPMC3163201 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.

Madar Daniel D Dekel Erez E Bren Anat A Alon Uri U

BMC systems biology 20110712

<h4>Background</h4>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-r ...[more]

PMID: 21749723

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Project description:UnlabelledGlucose is known to inhibit the transport and metabolism of many sugars in Escherichia coli. This mechanism leads to its preferential consumption. Far less is known about the preferential utilization of nonglucose sugars in E. coli. Two exceptions are l-arabinose and d-xylose. Previous studies have shown that l-arabinose inhibits d-xylose metabolism in Escherichia coli. This repression results from l-arabinose-bound AraC binding to the promoter of the d-xylose metabolic genes and inhibiting their expression. This mechanism, however, has not been explored in single cells. Both the l-arabinose and d-xylose utilization systems are known to exhibit a bimodal induction response to their cognate sugar, where mixed populations of cells either expressing the metabolic genes or not are observed at intermediate sugar concentrations. This suggests that l-arabinose can only inhibit d-xylose metabolism in l-arabinose-induced cells. To understand how cross talk between these systems affects their response, we investigated E. coli during growth on mixtures of l-arabinose and d-xylose at single-cell resolution. Our results showed that mixed, multimodal populations of l-arabinose- and d-xylose-induced cells occurred at intermediate sugar concentrations. We also found that d-xylose inhibited the expression of the l-arabinose metabolic genes and that this repression was due to XylR. These results demonstrate that a strict hierarchy does not exist between l-arabinose and d-xylose as previously thought. The results may also aid in the design of E. coli strains capable of simultaneous sugar consumption.ImportanceGlucose, d-xylose, and l-arabinose are the most abundant sugars in plant biomass. Developing efficient fermentation processes that convert these sugars into chemicals and fuels will require strains capable of coutilizing these sugars. Glucose has long been known to repress the expression of the l-arabinose and d-xylose metabolic genes in Escherichia coli. Recent studies found that l-arabinose also represses the expression of the d-xylose metabolic genes. In the present study, we found that d-xylose also represses the expression of the l-arabinose metabolic genes, leading to mixed populations of cells capable of utilizing l-arabinose and d-xylose. These results further our understanding of mixed-sugar utilization and may aid in strain design.

Dataset Information

Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.

Background

Results

Conclusions

Publications

Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.

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