Polymer Models of Yeast S. Cerevisiae Genome Organization

Abstract

Three-dimensional (3D) chromosomal organization impacts critical cellular processes including transcription, replication, and genomic stability. Despite the ubiquity of these challenges, a growing body of evidence suggests that major features of interphase chromosomal organization significantly vary across eukaryotes. A series of recent studies using optical and 3C-based experimental approaches has shown that on a global level the yeast genome is organized in a confined polymeric brush with the chromosomal centromeres tethered to the spindle pole body and telomeres tethered to the nuclear periphery. This happens to be in a striking difference with the human genomic organization, which chromosomes are shown to assume the fractal globule conformation with domains of active and inactive chromatin. In this work we investigated the implications of a Rabl-like chromosome organization using stochastic simulations of polymer dynamics and an exactly solvable polymer model. We showed that depending on the position along the genome, genomic loci are exposed to different mechanical stresses that may affect their biological function. This nonuniformity of the environment is especially prominent within a ∼100 kbp region around a centromere where the density effects statistically stretch the chromatin. We also found that a whole region of parameters describing the average state of the chromatin fiber was consistent with the experimental Hi-C data. Finally, the dynamical simulations showed that rapid progression through cell cycle allowed for spatial, but not necessarily topological, equilibration of yeast chromosomes, limiting their mutual entanglement.