Effect of Architecture of Cell Nucleus on the Folding Principles of 3D Genome of Budding Yeast

Abstract

Architecture of the cell nucleus and the spatial organization of genome are critical for nuclear functions. Single-cell imaging techniques and chromosome conformation capture (3C) based methods provide a wealth of information on the spatial organization of chromosomes. Computational tools for modeling chromosome structure have broad implications in studying effects of the geometry of nucleus on higher-order genome organization and nuclear functions. Here we describe a multi-chromosome constrained self-avoiding chromatin model for studying ensembles of structural genome models to understand the folding principles of budding yeast genome. We successfully generated a large number of model genomes of yeast under different geometrical constraints and found that spatial confinement of cell nucleus and molecular crowding in the nucleus are key determinants of the folding behavior of yeast chromosomes. Furthermore, the relative positioning of chromosomes and the interactions between them are found to be due to presence of nuclear landmarks such as centromere tethering to spindle pole body.