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bioRxiv · 10.1101/2025.03.17.643620

A Population Model Reveals Surprising Role of Stochastic Cell Division in Epigenetic Memory Systems

Klingel, V.·Graf, D.·Weirich, S.·Jeltsch, A.·Radde, N. E.
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Abstract

Epigenetic memory systems can store transient environmental signals in bacteria in form of DNA methylation patterns. A synthetic zinc finger protein (ZnF4) binds to the DNA in a methylation-dependent manner and represses the expression of the DNA methyltransferase CcrM. The ON-state of these systems is characterized by high CcrM expression, high methylation levels, and low ZnF4 binding, but the mechanisms ensuring long-term ON-state stability remain unclear. Measurements showed a gradual shift of cell populations from ON to OFF starting after about four days of cultivation. We use a hybrid modeling approach integrating flow-cytometry data and bulk 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 under varying growth conditions 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 about the mechanisms and timing of the ON/OFF switch in individual cells.

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Klingel, V., Graf, D., Weirich, S., Jeltsch, A., Radde, N. E.. 2025-03-20. A Population Model Reveals Surprising Role of Stochastic Cell Division in Epigenetic Memory Systems. https://doi.org/10.1101/2025.03.17.643620

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