Dynamical Modeling of Three-Dimensional Genome Organization in Interphase Budding Yeast

Abstract

Eukaryotic genome is organized in a set of chromosomes each of which consists of a chain of DNA and associated proteins. Processes involving DNA such as transcription, duplication, and repair, therefore, should be intrinsically related to the three-dimensional organization of the genome. In this article, we develop a computational model of the three-dimensional organization of the haploid genome of interphase budding yeast by regarding chromosomes as chains moving under the constraints of nuclear structure and chromatin-chromatin interactions. The simulated genome structure largely fluctuates with the diffusive movement of chromosomes. This fluctuation, however, is not completely random, as parts of chromosomes distribute in characteristic ways to form "territories" in the nucleus. By suitably taking account of constraints arising from the data of the chromosome-conformation-capture measurement, the model explains the observed fluorescence data of chromosome distributions and motions.

Topology, structures, and energy landscapes of human chromosomes

“…Many approaches start by mapping the contact frequencies onto preferred spatial distances between the corresponding genomic loci. The resulting distances can be directly used to construct a potential much like the associative memory models of protein folding (14). They can also be used as constraints to derive a unique chromosome structure using algorithms resembling NMR protein structure determination (15,16).…”

Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes

“…These studies in yeast have led to several predictions: the 3D position of a gene can be altered due to the presence of an NE tether positioned within 10 kb 11 ; removal of chromosomal tethers at the centromere increases chromosome mobility as quantified by its confinement radius 18 ; the presence of Chr-NE tethers affects the distribution of telomere-telomere distances 17 ; the position of chromosomes within the nucleus may be altered due to a combination of Chr-NE tethering and volume exclusion 12 ; and the distribution of distances between the spindle pole body and the silent mating locus depends on tethering at the telomere 11 . These results have motivated more complicated heterogeneous models to consider more numerous sets of experimentally identified Chr-NE attachments 5 .…”

“…Heterogeneous interaction models allow affinity for the NE to vary along the chromosome fiber; several Downloaded by [UQ Library] at 01: 10 15 June 2015 models have specifically investigated the effects of chromosome tethers positioned at the centromeres and telomeres 11,12,14,15,[17][18][19] . These studies in yeast have led to several predictions: the 3D position of a gene can be altered due to the presence of an NE tether positioned within 10 kb 11 ; removal of chromosomal tethers at the centromere increases chromosome mobility as quantified by its confinement radius 18 ; the presence of Chr-NE tethers affects the distribution of telomere-telomere distances 17 ; the position of chromosomes within the nucleus may be altered due to a combination of Chr-NE tethering and volume exclusion 12 ; and the distribution of distances between the spindle pole body and the silent mating locus depends on tethering at the telomere 11 .…”

“…In yeast, computational studies have considered a range of models differing in the number of attachments they consider 11,12,14,15,17,18 . Homogeneous interaction models assume all chromosome sites interact equally with the NE due to the complete presence or absence of attachments at all sites along the chromosome fiber 17 .…”

“…In recognition of this growing body of evidence, many computational studies of genome organization now incorporate the specific sites of Chr-NE attachment as model parameters [11][12][13][14][15][16][17] .…”