Depletion of CTCF and cohesin in regulatory domains reflects the topological segmentation of the genome. Tissue-invariant CTCF sites (bound in more than nine tissues) are significantly depleted (but not absent) in regulatory domains when considering all functionally defined regions (A). However, the statistical significance of this depletion becomes marginal if the comparison is limited to intervals included in TADs, and not compared against the overall genome (B). Constitutive cohesin complex-binding sites (data not shown), or CTCF/cohesin co-occupied regions (C) also showed only a slightly reduced density in RDs, when compared with the part of the genome that is included in TADs.
