What is it about?
Epigenetic cell memory ensures that cells are locked into specialized functions for the life-time of an organism. Phenotype loss is often associated with diseases, such as cancer, and is also required for artificially reprogramming cells from one type to another. The compaction of DNA, induced by histone modifications and DNA methylation, has recently appeared as a key mediator of epigenetic cell memory. However, a mechanistic understanding of how its dynamics affect the temporal duration of this memory is lacking. Here, we develop a model that includes these dynamics in gene regulation.
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Why is it important?
Our results show that when the auto and cross-catalysis of these modifications are sufficiently slower than DNA replication, loss of cell memory will occur. Our mathematical formulas show how the parameters capturing these time scales depend on the abundance of methyl-DNA-binding proteins, on writers, erasers, and readers of nucleosome modifications, and on cell division time. With this information, one may design experimental interventions to either enforce phenotypic plasticity or re-lock phenotypes in aberrant cells.
Perspectives
Working on this paper has been challenging, given the complicated models developed and the several analysis conducted. But the whole effort was rewarded by having contributed to such an important research. It is often not so obvious how mathematical tools can be exploited in fields such as systems and synthetic biology, but I hope that this work can help highlight how mathematical models and analyses are often essential to achieve a mechanistic understanding of biological processes.
Simone Bruno
Massachusetts Institute of Technology
Read the Original
This page is a summary of: Epigenetic cell memory: The gene’s inner chromatin modification circuit, PLoS Computational Biology, April 2022, PLOS,
DOI: 10.1371/journal.pcbi.1009961.
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