Extended Data Fig. 3: Global disruption of chromatin architecture upon CTCF loss.

a, APA on Hi-C peak loci (> 100-kb looping range) on convergent CTCF binding sites identified in control ESCs (n = 3185) and NPCs (n = 3686) and on Hi-C peak loci that have no CBSs (n = 2874 (ESCs), n = 2940 (NPCs). Scores on the bottom represent focal enrichment of peak pixel against pixels in its lower left. b, Aggregate boundary analysis showing average change in boundary strength between samples. Each triangle is a contact map of the difference in the average contact profile at TAD boundaries between two time points. The bottom column shows difference in the average boundary profile between the two control samples. c, Scatter plots of insulation scores at TAD boundaries in control and auxin treated ESCs (left) and NPCs (right). A higher score denotes lower insulation. d, Boxplots showing insulation scores at TAD boundaries that overlapped with housekeeping genes and CBSs, with other genes and CBSs, and TAD boundaries without CBSs in control and auxin treated ESCs and NPCs. All boxplots hereafter are defined as: Central bar, median; lower and upper box limits, 25th and 75th percentiles, respectively; whiskers, minimum and maximum value within the rage of (1st quartile-1.5*(3rd quartile- 1st quartile)) to (3rd quartile+1.5*(3rd quartile- 1st quartile)). *** p value < 0.001, two-tailed t-test. e, The number of TAD boundaries (left), stripes (middle), and insulated neighborhoods (INs) in control, CTCF-depleted, and auxin washout cells. Hatched bars indicate overlap with control cells. f, Hi-C contact frequencies at each genomic distance. g–i, Comparison of Hi-C datasets generated in this study and by Nora et al.¹³. Scatter plots of insulation scores at all TAD boundaries (g). Number of TAD boundaries in control and CTCF-depleted cells from both studies. Hatched bars indicate the overlap with control cells (h). Genome browser snapshots showing Hi-C contact heatmaps, TAD boundaries, directionality indices (DIs), and insulation scores analyzed in the two independent studies at the same genomic region in control and CTCF-depleted cells (i).