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Tuning cell differentiation patterns and single cell dynamics by regulating proteins’ functionalities in a toggle switch
Authors:Xiaofeng Dai   Shannon Healy   Olli Yli-Harja  Andre S. Ribeiro  
Affiliation:aComputational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, Finland;bCenter for Computational Physics, Coimbra University, P-3004-516 Coimbra, Portugal;cInstitute for Systems Biology, 1441N 34th St, Seattle, WA 98103-8904, USA
Abstract:We investigate how the regulation of protein multi-functionalities affect the dynamics of a stochastic model of a toggle switch and the differentiation pattern of cell population regulated by the switch. We study the effects of loss of functionality in DNA-binding and repression and the involvement in differentiation pathway choice. First is shown how the patterns of cell differentiation differ, when each of these functionalities is fully non-functional. Next, tuning the fraction of non-functional proteins regarding the ability to bind DNA is shown to allow fine tuning of the switch and cell differentiation pattern dynamics. Finally, biasing the probability of functionality of the two proteins biases the dynamics of the switch and cell differentiation patterns, especially when transcription factors retain the ability to bind DNA but have lost the ability to repress gene expression. Our results suggest that, besides transcriptional and translational levels of regulation, activation of functionalities in multi-functional proteins are an important regulator of gene networks.
Keywords:Functionality regulation   Toggle switch   Functional protein   Non-functional protein   Cell differentiation
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