Abstract
Interphase chromosomes in Saccharomyces cerevisiae are tethered to the nuclear envelope at their telomeres and to the spindle pole body (SPB) at their centromeres. Using a polymer model of yeast chromosomes that includes these interactions, we show theoretically that telomere attachment to the nuclear envelope is a major determinant of gene positioning within the nucleus only for genes within 10 kb of the telomeres. We test this prediction by measuring the distance between the SPB and the silent mating locus (HML) on chromosome III in wild–type and mutant yeast strains that contain altered chromosome-tethering interactions. In wild-type yeast cells we find that disruption of the telomere tether does not dramatically change the position of HML with respect to the SPB, in agreement with theoretical predictions. Alternatively, using a mutant strain with a synthetic tether that localizes an HML-proximal site to the nuclear envelope, we find a significant change in the SPB-HML distance, again as predicted by theory. Our study quantifies the importance of tethering at telomeres on the organization of interphase chromosomes in yeast, which has been shown to play a significant role in determining chromosome function such as gene expression and recombination.
Highlights
Chromosome organization during interphase Many different lines of experimental evidence have revealed that chromosomes in cells are organized in space and in time [1,2,3,4], and that this organization has a strong influence on chromosome functions such as gene expression, DNA-damage repair, recombination, and replication [4,5,6,7,8,9]
A valid chromosome configuration is any path of a random walker that begins 50 nm away from the north pole and ends at the surface of the sphere while remaining within the confines of the nucleus
Three-dimensional chromosome organization in the yeast nucleus provides a powerful model system for understanding the spatial organization-function relationship for eukaryotic genomes. Their spatial organization is described in quantitative detail by a random-walk polymer model that takes into account the tethering of the telomeres to the nuclear membrane and the centromeres to the spindle pole body
Summary
Chromosome organization during interphase Many different lines of experimental evidence have revealed that chromosomes in cells are organized in space and in time [1,2,3,4], and that this organization has a strong influence on chromosome functions such as gene expression, DNA-damage repair, recombination, and replication [4,5,6,7,8,9]. While distinct chromosome territories exist in the nucleus of higher eukaryotes [11,14,17,18], a highly intermingled yet polarized arrangement of chromosomes is prominent in the interphase nucleus of budding yeast, Saccharomyces cerevisiae [12,15,19]. Rabl was the first to describe this arrangement of chromosomes in salamander larvae cells in 1885 [20]. Its most prominent feature is the attachment of chromosomes at the nuclear envelope in a polarized fashion [21]. In budding yeast centromeres of all the chromosomes are attached via microtubules to the spindle pole body (SPB), which is a large protein complex in the nuclear envelope [22,23,24]. Chromosomes during interphase are tethered to the nuclear periphery at their telomeres through protein pathways that involve Yku, Yku, Sir, Esc, Mps, and Siz2 [25,26,27,28,29]
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