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| The EMBO Journal
(2001) 20, 2528–2535, doi:10.1093/emboj/20.10.2528 |
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| Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion |
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| Attila Becskei1, Bertrand Séraphin2 and Luis Serrano1 |
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1 European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69012 Heidelberg, Germany 2 Present address: CGM-CNRS, Avenue de la Terrasse, F-91198 Gif sur Yvette Cedex, France To whom correspondence should be addressed Attila Becskei, becskei@embl-heidelberg.de Received 4 October 2000; Revised 19 January 2001; Accepted 22 March 2001. |
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| Abstract |
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| Feedback is a ubiquitous control mechanism of gene networks. Here, we have used positive feedback to construct a synthetic eukaryotic gene switch in Saccharomyces cerevisiae. Within this system, a continuous gradient of constitutively expressed transcriptional activator is translated into a cell phenotype switch when the activator is expressed autocatalytically. This finding is consistent with a mathematical model whose analysis shows that continuous input parameters are converted into a bimodal probability distribution by positive feedback, and that this resembles analog–digital conversion. The autocatalytic switch is a robust property in eukaryotic gene expression. Although the behavior of individual cells within a population is random, the proportion of the cell population displaying either low or high expression states can be regulated. These results have implications for understanding the graded and probabilistic mechanisms of enhancer action and cell differentiation. |
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| Keywords: enhancer, genetic switch, graded response, stochastic, transcriptional activator |
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