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. Author manuscript; available in PMC: 2023 Mar 3.
Published in final edited form as: Mol Cell. 2022 Feb 18;82(5):1003–1020.e15. doi: 10.1016/j.molcel.2022.01.015

Figure 2: GSI-resistance restructures enhancer-promoter loops.

Figure 2:

(A) Pileup HiC maps at loops per interaction frequency change.

(B) Fraction of classes of genomic elements connected to differential loops. Enh: Enhancer, Pro: Promoter.

(C) HiC changes per quartile of differential H3K27ac on connected enhancers.

(D) Pileup HiC maps at SEs per H3K27ac change.

(E) Differential expression distribution per connected enhancer-promoter (EP) loop change.

(F) Differential expression per enhancer activity and EP contact change (Wilcoxon test).

(G) Left: Notch-bound (MAML1) E1 SE (magenta), Notch-unbound E2 SE (cyan) and MYC promoter (yellow) Oligopaint probes. Right: HiC signal between the noted probes.

(H) Bottom: distributions of distance between the noted elements in parental vs resistant cells (Wilcoxon test). Parental (resistant) MYC-E1 and MYC-E2 mean (+/− SD) distance: 0.399 (+/− 0.176) (0.407 (+/− 0.176)) and 0.401 (+/− 0.173) (0.389 (+/− 0.177)) μm. Top: representative cells. Blue: DAPI.

(I) MYC transcript (top), ICN1 and MYC protein (bottom) levels in DMSO- and GSI-treated parental, GSI-resistant, DMSO-treated reversed, and GSI-treated reversed DND41. Control: β-Actin.

(J) MYC-promoter-viewpoint UMI 4C-seq track (left), quantification (right, mean ± SD of 3 replicates) and H3K27ac per condition in (I) (t-test). NS: p>0.05.