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. Author manuscript; available in PMC: 2024 Nov 22.
Published in final edited form as: Cell. 2023 Nov 22;186(24):5269–5289.e22. doi: 10.1016/j.cell.2023.10.023

Figure 3. IKAROS regulates TAD and sub-TAD organization.

Figure 3.

(A) Size distribution of common and differential TADs. Red dashed line shows the median size of common TADs. (B) Differential aggregate TAD analysis (ATA) of TADs classified into split (1,2) and contracted (4) in IKDN or split in WT (3). WT-IKDN score is shown in all panels. A schematic of TADs in WT and IKDN is shown with the perspective employed for analysis shaded yellow. (2) subset of TADs in (1) with (Z1 > Z0). (3) Note absence of signal in the Z0 sector. (4) Filter X1>X0 reveals the subset of contracted TADs where loss of border-spanning contacts drives the shift. (C) Merged and split TADs at the Igκ locus. O/E Hi-C contacts and TAD calls for WT and IKDN. (D) Loss in CTCF hybrid loops leading to TAD boundary shift around the Blk locus (yellow stripe). (E) Aggregate regional analysis (ARA) of WT and IKDN O/E Hi-C signal at anchors of downregulated hybrid and structural CTCF HiChIP loops. Schematics illustrate the insulation and conduction properties of each anchor type. (F) ARA of WT and IKDN O/E Hi-C signal at enhancer and promoter anchors of downregulated H3K27ac HiChIP loops with or without CTCF (+ or −) binding. Schematics illustrate interactions between adjacent domains and potential mechanisms involved. (G) Aggregate WT and IKDN Hi-C signals of downregulated and upregulated hybrid and structural CTCF HiChIP loops. Difference between WT and IKDN aggregate signals is shown on the right. (H) Average ChIP-seq enrichment (RPM) at downregulated structural loop anchors and at internal decommissioned enhancers. (I) Model by which IKAROS organizes TADs. Source: Tables S2-3, S5.