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Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion
Author(s) -
Becskei Attila,
Séraphin Bertrand,
Serrano Luis
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.10.2528
Subject(s) - biology , positive feedback , enhancer , activator (genetics) , gene expression , saccharomyces cerevisiae , population , negative feedback , gene regulatory network , gene , regulation of gene expression , cell , microbiology and biotechnology , genetics , computational biology , physics , demography , quantum mechanics , voltage , sociology , electrical engineering , engineering
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.