Impact of chromosome fusions on 3D genome organization and gene expression in budding yeast

ABSTRACT The three-dimensional organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remains debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization and global gene expression in budding yeast containing chromosome fusions. We used computational modelling and single cell imaging to determine chromosome position and integrated these data with genome-wide transcriptional profiles from RNA sequencing. We find that chromosome fusions dramatically alter 3D nuclear organization without leading to strong genome-wide changes in transcription. However, we observe a mild but significant and reproducible increase in expression of genes near fusion sites. Modeling suggests that this is due to both disruption of telomere-associated silencing and the displacement of genes relative to the nuclear periphery. A 10% decrease in the predicted time a gene spends near the nuclear periphery is associated with a 10% increase in expression. These data suggest that basal transcriptional activity is sensitive to radial changes on gene position, and provide insight into the functional relevance of budding yeast chromosome-level three-dimensional organization in gene expression.