Controlled exchange of chromosomal arms reveals principles driving telomere interactions in yeast

Abstract

The 32 telomeres in the budding yeast genome cluster in three to seven perinuclear foci. Although individual telomeres and telomeric foci are in constant motion, preferential juxtaposition of some telomeres has been scored. To examine the principles that guide such long-range interactions, we differentially tagged pairs of chromosome ends and developed an automated three-dimensional measuring tool that determines distances between two telomeres. In yeast, all chromosomal ends terminate in TG 1-3 and middle repetitive elements, yet subgroups of telomeres also share extensive homology in subtelomeric coding domains. We find that up to 21 kb of >90% sequence identity does not promote telomere pairing in interphase cells. To test whether unique sequence elements, arm length, or chromosome territories influence juxtaposition, we reciprocally swapped terminal domains or entire chromosomal arms from one chromosome to another. We find that the distal 10 kb of Tel6R promotes interaction with Tel6L, yet only when the two telomeres are present on the same chromosome. By manipulating the length and sequence composition of the right arm of chr 5, we confirm that contact between telomeres on opposite chromatid arms of equal length is favored. These results can be explained by the polarized Rabl arrangement of yeast centromeres and telomeres, which promote to telomere pairing by allowing contact between chromosome arms of equal length in anaphase.

Keep moving and stay in a good shape to find your homologous recombination partner

“…This organization largely favours interaction between centromeric proximal sequences as well as contact between subtelomeres (Bystricky et al 2005;Schober et al 2008;Therizols et al 2010;Duan et al 2010;Agmon et al 2013). Consistently, recombination between centromeres on one hand and between subtelomeric sequences on the other hand occurs efficiently (Burgess and Kleckner 1999;Brown et al 2010;Agmon et al 2013;Lee et al 2016).…”

Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions

“…These single structures have been used to make inferences about the organization of the respective genomes. 6,9 Microscopic studies show considerable variation in the distances between pairs of loci within populations of cells 10,11,13 and…”

“…6,8,9 These studies resulted in the proposal of unique genome conformations that do not represent the dynamic nature of nuclear organization. However, it is important to incorporate dynamism because genome organization shows a lot of variability [10][11][12] indicating that it must change from cell to cell and over time. Critically, the chromosomal interactions identified by proximity-based ligation are averaged across the test cell population and the subset of interactions that is present in a single cell cannot be determined.…”

High-throughput chromatin motion tracking in living yeast reveals the flexibility of the fiber throughout the genome

“…Structural data obtained by statistical positioning of a gene in a yeast cell population led to a surprisingly simple model to define yeast nuclear architecture (Zimmer and Fabre 2011): Chromosome position can be predicted by a few parameters such as genomic arm length, telomeres (TEL), and centromeres (CEN) tethered to the NE via nuclear-envelope-tethered proteins and to the SPB via microtubules, respectively (Bystricky et al 2005;Therizols et al 2010;Zimmer and Fabre 2011). This description was recently complemented by the first Hi-C comprehensive maps (Rodley et al 2009;Duan et al 2010), which confirmed an organization guided by nuclear landmarks, including TEL that congregate in foci (Gotta et al 1996;Schober et al 2008). Recent Brownian dynamics (BD) simulations confirmed this structural model by recapitulating Hi-C and imaging data, assuming that physical tethering at TEL and CEN and volume exclusion were driving chromosome conformations (Tjong et al 2012;Wong et al 2012).…”