2381/11955648.v1 Yan Li Yan Li Judith HI Haarhuis Judith HI Haarhuis Angela Sedeno Cacciatore Angela Sedeno Cacciatore Roel Oldenkamp Roel Oldenkamp Marjon S van Ruiten Marjon S van Ruiten Laureen Willems Laureen Willems Hans Teunissen Hans Teunissen Kyle W Muir Kyle W Muir Elzo de Wit Elzo de Wit Benjamin D Rowland Benjamin D Rowland Daniel Panne Daniel Panne The structural basis for cohesin-CTCF-anchored loops University of Leicester 2020 Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics FULLY-AUTOMATIC CHARACTERIZATION HI-C REVEALS DATA-COLLECTION 3D GENOME WAPL CHROMOSOMES RESOLUTION MECHANISM TOPOLOGY DOMAINS 2020-03-27 09:57:34 Journal contribution https://figshare.le.ac.uk/articles/journal_contribution/The_structural_basis_for_cohesin-CTCF-anchored_loops/11955648 Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2–SCC1 subunits of human cohesin. We report a crystal structure of SA2–SCC1 in complex with CTCF at a resolution of 2.7 Å, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF.