The three-dimensional organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects is still controversial. 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 growth-rate neutral 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. Chromosome displacement relative to the nuclear periphery has mild but widespread and significant effects on transcription. A 10% decrease in the time a gene spends near the nuclear periphery leads to a 10% increase in gene expression. Our study shows that basal transcriptional activity is sensitive to radial changes on chromosomal position, and provides support for the functional relevance of budding yeast chromosome-level three-dimensional organization in gene expression.

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