Work

A population model reveals a surprising role of stochastic cell division in epigenetic memory systems

Year: 2025

Type: article

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.

Source: iScience

DOI: 10.1016/j.isci.2025.113431

Authors: Viviane Klingel, Dimitri Graf, Sara Weirich, Albert Jeltsch, Nicole E. Radde

Institution: University of Stuttgart

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,240

Funders: Deutsche Forschungsgemeinschaft, Stuttgart Center for Simulation Science, Universität Stuttgart