a, Schematic of a Hi-C matrix displaying DNA–DNA contacts across a genomic region that includes two TADs. TADs in general are flanked by inwards-pointing CTCF sites (magenta arrows). Signal close to the diagonal line reflects short-range contacts, and contacts that span longer distances are found further away from the diagonal. The contacts within a TAD are formed by cohesin complexes (blue circles). Cohesin builds loops that it can enlarge until it encounters CTCF. Some TADs are enriched for contacts between the two CTCF sites that lie at their boundaries. These contacts are referred to as CTCF-anchored loops. b, Aggregate TAD analysis depicting the average contact frequency across TADs defined in wild-type cells. c, Heat map of the insulation score61 at TAD borders, as defined for wild-type cells. d, Aggregate peak analysis as in Fig. 3c, using two independent library preparations per genotype. e, Aggregate TAD analysis for wild-type and CTCFY226A/F228A cells as in b. f, Heat map of insulation scores at TAD borders for wild-type and CTCFY226A/F228A cells as in c.