TY - JOUR T1 - Generation of dynamic three-dimensional genome structure through phase separation of chromatin JF - bioRxiv DO - 10.1101/2021.05.06.443035 SP - 2021.05.06.443035 AU - Shin Fujishiro AU - Masaki Sasai Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/07/2021.05.06.443035.abstract N2 - Three-dimensional genome organization plays a critical role in DNA function. Flexible chromatin structure suggested that the genome is phase-separated to form A/B compartments in interphase nuclei. Here, we examined this hypothesis by developing a polymer model of the whole genome of human cells and assessing the impact of phase separation on genome structure. Upon entry to the G1 phase, the simulated genome expanded according to heterogeneous repulsion among chromatin chains, which moved chromatin heterogeneously, inducing phase separation. This repulsion-driven phase separation quantitatively reproduces the experimentally observed chromatin domains, A/B compartments, lamina-associated domains, and nucleolus-associated domains, consistently explaining nuclei of different human cells and predicting their dynamic fluctuations. We propose that phase separation induced by heterogeneous repulsive interactions among chromatin chains largely determines dynamic genome organization.One-Sentence Summary The whole-genome simulation showed the importance of repulsion-driven phase separation of chromatin in genome organization.Competing Interest StatementThe authors have declared no competing interest. ER -