The Taub Faculty of Computer Science Events and Talks

While it has been long recognized that genes are not randomly disposed along the genome, the degree to which the three dimensional (3D) structure of the genome influences the arrangement of genes has remained elusive. In particular, 'transcriptional-factories' are thought to lead to the positioning co-regulated genes in physical proximity, however there have also been reports to the contrary. Here we present evidence that the co-localization of yeast genes regulated by the same factor is far greater when observed spatially than the genomic gene order. We first provide a minimum-assumption method for the interpolation and embedding of chromosome-conformation capture data. Next, we introduce a statistical framework that enables the comparison of the spatial and genomic densities of any given set of genes. For 68 out of 117 examined transcription factors we observe a significant enrichment of the their targets at the spatial scale that is far more widespread than the enrichment detected at the genomic linear gene order. Furthermore, we found that transcription factors with highly spatially co-localized targets are significantly more highly expressed in the specific conditions that the genomic structure was determined, validating activity related to the observed target density. Overall, our results provide robust evidence for a general organization of the genome into co-regulated spatially-restricted units.