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Published on: March 10, 2016
A population model reveals a surprising role of stochastic cell division in epigenetic memory systems
Viviane Klingel1, Dimitri Graf2, Sara Weirich2
1Institute for Stochastics and Applications, University of Stuttgart, Wankelstrase 5, 70563 Stuttgart, Germany.
Abstract:
Epigenetic memory systems store transient environmental signals in bacteria in specific DNA methylation patterns. Synthetic zinc finger protein (ZnF4) binds to the DNA in a methylation-dependent manner and represses the expression of the DNA methyltransferase CcrM. The mechanisms ensuring long-term ON-state stability remain unclear. Measurements showed a gradual shift of cell populations from ON to OFF starting after four days of cultivation. We use a hybrid modeling approach integrating flow cytometry data and bulk DNA methylation measurements to test the hypothesis that stochastic cell division is a key factor in this transition. Interestingly, model parameters cluster into two groups with opposite effects of cell division rates on ON-state stability. Experiments show that faster cell division increases memory stability-an initially unexpected result. Model simulations provide a potential explanation for this observation and deepen our understanding of the mechanisms and timing of the ON/OFF switch in individual cells.
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