Regulation of pericentromeric repeat copy number by EMT factors

Although the length and sequence composition of pericentromeric repeats vary widely across eukaryotes, the presence of multiple such repeats remains a conserved feature of eukaryotic chromosomes. Pericentromeric heterochromatin is frequently misregulated in human diseases, contributing to genomic instability, particularly through the expansion of these repeats in solid tumors. Previously, we developed a mathematical model to track the dynamics of pericentromeric repeats, including H3K9me-mediated silencing, long non-coding RNAs (lncRNAs), and repeat copy number. In this study, we analyze single-cell RNA sequencing data and integrate our quantitative model with epithelial-mesenchymal transition (EMT) factors. We identify EMT factors such as Snail and Zeb1 as critical regulators of repeat copy number. Our findings highlight a delicate interplay between pericentromeric repeats and chromatin-regulating factors, suggesting that shifts in EMT factor expression can drive large-scale repeat expansion.