Document Type
Article
Original Publication Date
2024
Journal/Book/Conference Title
PLOS Computational Biology
Volume
20
Issue
4
DOI of Original Publication
10.1371/journal.pcbi.1012027
Date of Submission
May 2024
Abstract
Although the length and constituting sequences for pericentromeric repeats are highly variable across eukaryotes, the presence of multiple pericentromeric repeats is one of the conserved features of the eukaryotic chromosomes. Pericentromeric heterochromatin is often misregulated in human diseases, with the expansion of pericentromeric repeats in human solid cancers. In this article, we have developed a mathematical model of the RNAi-dependent methylation of H3K9 in the pericentromeric region of fission yeast. Our model, which takes copy number as an explicit parameter, predicts that the pericentromere is silenced only if there are many copies of repeats. It becomes bistable or desilenced if the copy number of repeats is reduced. This suggests that the copy number of pericentromeric repeats alone can determine the fate of heterochromatin silencing in fission yeast. Through sensitivity analysis, we identified parameters that favor bistability and desilencing. Stochastic simulation shows that faster cell division and noise favor the desilenced state. These results show the unexpected role of pericentromeric repeat copy number in gene silencing and provide a quantitative basis for how the copy number allows or protects repetitive and unique parts of the genome from heterochromatin silencing, respectively.
Rights
© 2024 Ghimire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Recommended Citation
Ghimire P, Motamedi M, Joh R (2024) Mathematical model for the role of multiple pericentromeric repeats on heterochromatin assembly. PLoS Comput Biol 20(4): e1012027. https://doi.org/10.1371/journal.pcbi.1012027
Is Part Of
VCU Physics Publications
Comments
Originally published at https://doi.org/10.1371/journal.pcbi.1012027