Rabl Organization of Chromosomes in the Yeast Nucleus

Abstract

The location of genes in the interphase nucleus can influence gene expression and recombination. We examine a random walk polymer model of an interphase yeast chromosome that takes into account Rabl organization, namely attachment of the centromere to the spindle pole body, and tethering of the telomeres to the nuclear membrane. using this model, we calculate the probability distribution for the spatial positioning of a single genetic locus on chromosome III and compare it to an experimental distribution obtained by fluorescence microscopy of wild-type yeast cells. To best fit the model to the experimental distribution, the parameters for chromatin rigidity and nuclear architecture are optimized using values within the ranges reported by previous studies. We then quantitatively test the model using a yeast mutant in which the telomeres are not tethered to the nuclear envelope. The mutant's experimental and computational distributions quantitatively agree, which is evidence that a random walk polymer model of yeast chromosomes that incorporates Rabl organization can account for the spatial positioning of genetic loci during interphase. Further studies will apply this model to the understanding of homologous recombination, specifically in the context of double strand break repair.