Fig. 3: NIPBL partial loss leads to a decrease in hierarchical TAD structures and preferentially affects CTSSs residing in high-level hierarchical TADs.
From: Disruption of TAD hierarchy promotes LTR co-option in cancer
a, Representative hierarchical TAD structures by Hi-C contact maps (10 kb resolution) under control and NIPBL perturbation conditions in melanoma cells. TADs are organized as singletons (navy blue arrows) or hierarchical structures characterized by nested sub-TADs (green arrows) and nested inside meta-TADs (light blue arrows). NIPBL downregulation weakened TAD structures and preferential loss of outermost TADs (light blue arrows) of hierarchical TADs. n = 2 biological replicates. b–d, The effects on hierarchical TAD structures by partial loss of NIPBL in melanoma cells, including on the number of various levels of hierarchical TAD structures by OnTAD (b), size distribution (c) and TAD boundary/insulation scores (d). ****P < 0.0001, Mann–Whitney two-tailed unpaired nonparametric t test. e, Comparison of fraction of baseline CTSS versus differentially regulated CTSSs by shNIPBL_1 and shNIPBL_2 in hierarchical and nonhierarchical TADs defined under control condition (≥ level 3 versus ≤ level 2 and singleton). *P < 0.05, **P < 0.01, two-tailed chi-square test. Number of CTSS in each category is in Extended Data Fig. 7. f,g, Relative CTSS distance to nearest TAD boundaries defined in shLuc condition (f) and in shNIPBL condition (g). The relative CTSS distance to TAD boundaries was calculated as the distance of CTSS to the nearest TAD boundary divided by the size of the respective TAD defined in the shLuc and shNIPBL conditions. h, Schematics illustrating the change in location of CTSSs relative to TAD structure changes with NIPBL perturbation. diff. CTSS, differential CTSS.
