Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion
AUTOR(ES)
Becskei, Attila
FONTE
Oxford University Press
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=125456Documentos Relacionados
- Are binary synapses superior to graded weight representations in stochastic attractor networks?
- Modeling molecular networks: a systems biology approach to gene function
- Cell signaling can direct either binary or graded transcriptional responses
- Complex networks: the key to systems biology
- Biological networks: from physical principles to biological insights