Fig. 7: Genome-wide differential hub screen identifies loci that are aberrantly folded and expressed in ibrutinib-resistant MCL.
From: Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance
a Scatter plot showing log2 fold change of hub interactivity in ibrutinib-resistant Rec-1 vs. hub interaction counts in ibrutinib-sensitive cells. Dotted lines mark enhancer-promoter hubs with ≥ 2-fold decrease (“less interacting in ibrutinib resistance”) or increase (“more interacting in ibrutinib resistance”) in interaction counts in ibrutinib-resistant vs. ibrutinib-sensitive Rec-1 cells. Selected hubs are labeled. b Box-and-whisker plots comparing ATAC-seq (left), H3K27ac ChIP-seq (center), and RNA-seq (right) of hubs with marked loss of interactivity in ibrutinib-resistant cells. Box-and-whisker plots: center line, median; box limits, upper (75th) and lower (25th) percentiles; whiskers, 1.53 interquartile range (n = 34). P-value: two-tailed Wilcoxon rank sum test. c Box-and-whisker plots comparing ATAC-seq (left), H3K27ac ChIP-seq (center), and RNA-seq (right) in hubs that gained interactivity in ibrutinib-resistant cells. Box-and-whisker plots: center line, median; box limits, upper (75th) and lower (25th) percentiles; whiskers, 1.53 interquartile range (n = 125). P-value: two-tailed Wilcoxon rank sum test. d Concordant changes in ATAC-seq, H3K27ac ChIP-seq, RNA-seq, and Hi-C over the PTPRG locus between ibrutinib-sensitive and ibrutinib-resistant Rec-1 cells. e PTPRG normalized RNA-seq reads in ibrutinib-sensitive and ibrutinib-resistant cells. Each dot represents a biological replicate (n = 3). P-value: two-sided t-test; error bars: ± SEM. f Normalized Hi-C contact maps in ibrutinib-resistant (upper triangle) and ibrutinib-sensitive (lower triangle) Rec-1 cells at the PTPRG hub locus. g Coordinated changes in ATAC-seq, H3K27ac ChIP-seq, RNA-seq, and Hi-C over the BCL2L1 locus between ibrutinib-sensitive and ibrutinib-resistant Rec-1 cells. h BCL2L1 normalized RNA-seq reads in ibrutinib-sensitive and ibrutinib-resistant cells. Each dot represents a biological replicate (n = 3). P-value: two-sided t-test; error bars: ± SEM. i Normalized Hi-C contact maps in ibrutinib-resistant (upper triangle) and -sensitive (lower triangle) Rec-1 cells at the BCL2L1 hub.
