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Enhancement of cellular memory by reducing stochastic transitions

Acar, Murat and Becskei, Attila and van Oudenaarden, Alexander. (2005) Enhancement of cellular memory by reducing stochastic transitions. Nature, 435 (7039). pp. 228-232.

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Official URL: http://edoc.unibas.ch/46413/

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Abstract

On induction of cell differentiation, distinct cell phenotypes are encoded by complex genetic networks. These networks can prevent the reversion of established phenotypes even in the presence of significant fluctuations. Here we explore the key parameters that determine the stability of cellular memory by using the yeast galactose-signalling network as a model system. This network contains multiple nested feedback loops. Of the two positive feedback loops, only the loop mediated by the cytoplasmic signal transducer Gal3p is able to generate two stable expression states with a persistent memory of previous galactose consumption states. The parallel loop mediated by the galactose transporter Gal2p only increases the expression difference between the two states. A negative feedback through the inhibitor Gal80p reduces the strength of the core positive feedback. Despite this, a constitutive increase in the Gal80p concentration tunes the system from having destabilized memory to having persistent memory. A model reveals that fluctuations are trapped more efficiently at higher Gal80p concentrations. Indeed, the rate at which single cells randomly switch back and forth between expression states was reduced. These observations provide a quantitative understanding of the stability and reversibility of cellular differentiation states.
Faculties and Departments:05 Faculty of Science
05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Synthetic Microbiology (Becskei)
UniBasel Contributors:Becskei, Attila
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Macmillan
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Nov 2017 08:22
Deposited On:23 Nov 2017 08:22

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