Chromosome conformation capture approaches have shown that interphase chromatin 
is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized 
topological domains. This compartmentalization is thought to facilitate the 
matching of genes and regulatory elements, but its precise function and 
mechanistic basis remain unknown. Cohesin controls chromosome topology to enable 
DNA repair and chromosome segregation in cycling cells. In addition, cohesin 
associates with active enhancers and promoters and with CTCF to form long-range 
interactions important for gene regulation. Although these findings suggest an 
important role for cohesin in genome organization, this role has not been 
assessed on a global scale. Unexpectedly, we find that architectural 
compartments are maintained in noncycling mouse thymocytes after genetic 
depletion of cohesin in vivo. Cohesin was, however, required for specific 
long-range interactions within compartments where cohesin-regulated genes 
reside. Cohesin depletion diminished interactions between cohesin-bound sites, 
whereas alternative interactions between chromatin features associated with 
transcriptional activation and repression became more prominent, with 
corresponding changes in gene expression. Our findings indicate that 
cohesin-mediated long-range interactions facilitate discrete gene expression 
states within preexisting chromosomal compartments.