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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 <jats:italic>Escherichia coli<\/jats:italic>, in which negative auto-regulation is part of a complex regulatory network.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We find that when negative auto-regulation is disrupted by placing the regulator <jats:italic>araC<\/jats:italic> 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 <jats:italic>n<\/jats:italic> = 1 with negative auto-regulation, to about <jats:italic>n<\/jats:italic> = 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Here we demonstrate that the negative auto-regulation motif in the native arabinose system of <jats:italic>Escherichia coli<\/jats:italic> 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-5-111","type":"journal-article","created":{"date-parts":[[2011,7,13]],"date-time":"2011-07-13T06:23:32Z","timestamp":1310538212000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli"],"prefix":"10.1186","volume":"5","author":[{"given":"Daniel","family":"Madar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erez","family":"Dekel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anat","family":"Bren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uri","family":"Alon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,7,12]]},"reference":[{"key":"726_CR1","doi-asserted-by":"crossref","DOI":"10.1201\/9781420011432","volume-title":"An Introduction to Systems Biology: Design Principles of Biological Circuits","author":"U Alon","year":"2006","unstructured":"Alon U: An Introduction to Systems Biology: Design Principles of Biological Circuits. 2006, Chapman and Hall\/CRC, 1,","edition":"1"},{"key":"726_CR2","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/ng881","volume":"31","author":"SS Shen-Orr","year":"2002","unstructured":"Shen-Orr SS, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. 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