The length and strength of compartmental interactions are modulated by condensin II activity.

The spatial organization of the genome is crucial for its function and integrity. Although the ring-like SMC complex condensin II has a well-documented role in organizing mitotic chromosomes, its function in interphase chromatin structure has remained more enigmatic. Using a combination of Oligopaint fluorescence in situ hybridization (FISH) and Hi-C, we show that altering condensin II levels in diploid Drosophila cells significantly changes chromosome architecture at large length scales between chromatin compartments. Notably, condensin II overexpression disrupts the robust boundary between heterochromatin and euchromatin, leading to interactions that span entire chromosomes. These interactions occur independent from transcriptional changes, suggesting that the mechanisms driving compartment formation and their interactions might be distinct aspects of genome organization. Our results provide new insights into the dynamic nature of chromosome organization and underscore the importance of condensin II in maintaining genomic stability.