Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes

CTCF clustering at domain boundaries is maximal at the scale of TADs. (A) CTCF enrichment at domain boundaries is widespread among the folding hierarchy in mouse ES cells. However, maximal enrichment occurs at 65% RI, where it is slightly higher compared to TADs identified by directionality index analysis (diTADs). (B) Domains at 65% are slightly smaller than diTADs identified on the same data set. (C) CTCF enrichment at domain boundaries in NPCs and CH12 cells shows a similar trend as in ESCs, with maxima located at 58% and 82% RI in NPCs and CH12, respectively. (D) The number and size of domains defined by maximal CTCF enrichment at boundaries are similar in ESCs, NPCs, and CH12 cells.