GSE33018
Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions
In recent years there has been considerable and growing interest in the 3-dimensional organization of genomes. In yeast this has included detailed FISH studies that show a surprising degree of spatial clustering of the tRNA genes, the localization of telomeres, centromere positioning, and global studies of chromosomal interactions. In this study we performed an integrated biophysical – molecular study to produce the first high-resolution 3-dimensional reconstruction of a eukaryotic genome from first principles. Our conformations were produced using a using a molecular dynamics simulator to model the 16 yeast chromosomes as individual polymers. Critically, the compaction, folding and spatial organization of these chromosomes was informed by empirical data determined using proximity-based ligation. Our models allow us to investigate the structural organization and functional spatial clustering of the yeast nucleus at a resolution that has not previously been possible. We clearly show that yeast chromosomes have preferred yet non-exclusive positions. Surprisingly, while there are general trends relating chromosome position along the spindle pole body – nucleolus axis and chromosome size, some chromosomes have territories that contain two linked domains. Similarly, there is clear evidence for functional clustering of tRNAs and Gal4 protein binding sites. Intriguingly, these functional clusters are dynamic and the identity of the component elements alters in different model solutions. Overall design: Genome Conformation Capture has been performed on exponentially growing Saccharomyces cerevisiae in media containing Glucose