Contrasting the organization and dynamics in normal and cancer cell chromosomes

Chromatin is organized into multiple domains, such as phase-separated compartments and topologically associating domains (TADs). Although the role of TADs in gene regulation is still unclear, it has been shown that there are differences between normal and cancer cells. Hi-C experiments show that sizes and epigenetic states are different between normal and cancer cells. We used the knowledge-based potential in Chromosome Copolymer Model (CCM) to generate the structural ensemble of chromatin. We simulated the structures of chromosomes 12 and 15 in RWPE1 and C42B cell lines. We first demonstrate that the structures from simulations are in agreement with the structures from Hi-C (using HIPPS) at the resolution of TADs. In particular, for the TAD regions that differ in the Hi-C contact maps between normal and cancer cells, we found that the distributions of locus pair distance and radius of gyration obtained from the simulations show the differences qualitatively consistent with those expected from the Hi-C data. We highlight that these structural differences lead to the dynamical changes in the given TAD regions, which are possibly connected with the differences in gene expression levels between normal and cancer cells.