Cohesin residency determines chromatin loop patterns

The organization of chromatin into higher-order structures is essential for chromosome segregation, the repair of DNA damage, and the regulation of gene expression. These structures are formed by the evolutionarily conserved SMC (structural maintenance of chromosomes) complexes. By analyzing synchronized populations of budding yeast with Micro-C, we observed that chromatin loops are formed genome-wide, and are dependent upon the SMC complex, cohesin. We correlated the loop signal with the position and intensity of cohesin binding to chromosomes in wild-type and cells depleted for the cohesin regulators Wpl1p and Pds5p. We generate a model to explain how the genomic distribution and frequency of loops are driven by cohesin residency on chromosomes. In this model a dynamic pool of cohesin with loop extrusion activity stops when encounters two regions occupied by stably bound cohesin, forming a loop. Different regions are occupied by cohesin in different cells, defining different patterns of chromatin loops. We mapped the 3D genome organization of mitotic chromatin in budding yeast (A364 background) by using Micro-C. We performed two replicates of Micro-C experiments for wild-type, Mcd1-AID, Brn1-AID, Wpl-AID, and one replicate for Pds5-AID cells. Time-course experiments were done in two replicates at 23°C and 30°C, respectively. The Micro-C contact matrices were stored into the formats for HiGlass (.mcool) or Juicer (.hic) 3D genome browsers.