In recent years, it has become evident that the spatial organisation of the genome is key for its function. This depends on a number of factors, including the cohesin protein complex. This essential complex is present in the cells in two versions that contain either the SA1 or SA2 subunit. Scientists at the Spanish National Cancer Research Centre (CNIO), the Centre for Genomic Regulation (CRG), and the Centro Nacional de Análisis Genómico (CNAG-CRG) have addressed the functional specificity of these two variant cohesin complexes. The study, published in Nature Structural and Molecular Biology, analyzes in-depth the functions of both variants in the 3-D genome architecture and shows how the alteration of SA2 influences gene expression and may favour the loss of differentiation in tumour cells.