DYNAMIC CHANGES IN 3D CHROMATIN STRUCTURE DURING EMT IN OVARIAN CANCER

Abstract

Epithelial-mesenchymal transition (EMT) describes the process by which polarized epithelial cells convert into mobile mesenchymal cells. Various experimental models of inducing EMT in cancer cells have shown epigenetic reprogramming between the epithelial and mesenchymal states but the accompanying adaptations of the genome architecture were not addressed. We hypothesized that there are genome-wide 3D chromatin changes between the epithelial and mesenchymal states in ovarian cancer during EMT. By integrating Hi-C with genome-wide epigenetic and transcriptomic profiles in ovarian cancer cell lines, it was observed that compartmentalization of the 3D genome plays a contributory role in the regulation of EMT genes. In addition, it was demonstrated that TADs regulate EMT genes via the insulation of the epithelial genes from its neighbouring regions, or via systemic chromatin loops between the regulatory elements and mesenchymal genes. Finally, using single-cell Hi-C, we demonstrated the fluid changes in the EMT TADs hubs at the cellular level.