The dynamic three-dimensional organization of the diploid yeast genome

Abstract

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it is unclear how homolog pairing in diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation using a polymer model, we observe significant homolog proximity that increases in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1-TDA1 alleles specifically under galactose induction and saturated growth. This pairing is accompanied by relocalization to the nuclear periphery and requires Nup2, suggesting a role for nuclear pore complexes. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization.DOI: http://dx.doi.org/10.7554/eLife.23623.001

Computational methods for analyzing and modeling genome structure and organization

“…The budding yeast genome organization has been well studied by microscopy (Berger et al, 2008;Bystricky, Laroche, van Houwe, Blaszczyk, & Gasser, 2005;Jin, Fuchs, & Loidl, 2000;Schober et al, 2008;Therizols, Duong, Dujon, Zimmer, & Fabre, 2010) and chromosome conformation capture (Dekker et al, 2002;Duan et al, 2010;Kim et al, 2017;Rodley, Bertels, Jones, & Sullivan, 2009). These experimental studies suggest that the budding yeast chromosomes are folded into the socalled Rabl configuration: The chromosome arms emanate from the spindle pole body where the centromeres cluster.…”

The biology and polymer physics underlying large‐scale chromosome organization

“…[116][117][118] This configuration results in an alignment of chromosome arms and increased intrachromosomal contacts that are more frequent near centromeres and to a lesser extent near telomeres, and on this basis have sometimes been referred to as territories. [119][120][121][122][123][124][125] In addition, it is important to stress the fact that the yeast chromosomes are much smaller than human chromosomes. As mentioned earlier, unlike for yeast cells, the equilibration time of human chromosomes is many orders of magnitude longer than the cell cycle 43…”

Forces driving the three‐dimensional folding of eukaryotic genomes

“…On the basis of this new knowledge, whole-genome conformation studies have been used to decipher how development or developmental disease (Dixon et al, 2015;Fraser et al, 2015;Lupiáñ ez et al, 2015;Franke et al, 2016;Bonev et al, 2017), cancer (Flavahan et al, 2016;Taberlay et al, 2016;Hnisz et al, 2017;Wu et al, 2017), DNA damage (Aymard et al, 2017;Canela et al, 2017), cellular aging (Criscione et al, 2016), and genetic variation (Javierre et al, 2016) impact on the structure and function of the genome. Needless to say that the advent of 3C technology (see overview in has also provided insights into the higher order genomic organization of bacteria (e.g., Le & Laub, 2016;Lioy et al, 2018), fungi (e.g., Mizuguchi et al, 2014;Kim et al, 2017;Tanizawa et al, 2017), nematodes (e.g., Crane et al, 2015), the Plasmodium falciparum parasite (Ay et al, 2014), and plants (e.g., Dong et al, 2017). It is noteworthy that A-/B-compartments and TAD-like structures can largely be identified across all organisms investigated to date.…”