The spatial organization of the chromosomes is crucial for gene expression and development. Inter-and intrachromosomal interactions form a crucial part of this epigenomic regulatory system. Here we use circular chromosome conformation capture-on-chip (4C) to identify interactions between repetitive and non-repetitive loci within the yeast genome. The interacting regions occur in non-randomly distributed clusters. Furthermore, the SIR2 histone deacetylase has opposing roles in the organization of the inter-or intrachromosomal interactions. These data establish a dynamic domain model for yeast genome organization. Moreover, they point to the repeated elements playing a central role in the dynamic organization of genome architecture.