Modeling the Effect of Histone Methylation on Chromosomal Organization in Colon Cancer Cells

Loop extrusion and compartmentalization are the two most important processes regulating the high-level organization of DNA in the cell nucleus. These processes are largely believed to be independent and competing (Sanborn et al. 2015; Nuebler et al. 2018). Chromatin consists of nucleosomes, which contain coils of DNA wrapped around histone proteins. Besides packing DNA, nucleosomes contain an “epigenetic code” tails of histone proteins are chemically modified at certain positions to leave certain “histone marks” on the chromatin fiber. This paper explores the effect of the H3K9me3 histone modification, which typically corresponds to inactive and repressed chromatin, on genome structure. Interestingly, in H3K9me3 domains, there are much fewer topologically associating domains (TADs) than in other domains, and there is a unique compartmentalization pattern. A high-resolution polymer model simulating both loop extrusion and compartmentalization is created to explore these differences.