Fig. 6
From: Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation
T-ALLgained CTCF binding facilitates oncogenic NOTCH1 transcriptional activity. a Scatter plot of CTCF sites in T-ALL quantifying CTCF level changes in GSI and GSI washout experiment. Differential CTCF ChIP-seq signal (log2 fold change) in GSI washout vs. GSI (y-axis) is plotted against differential CTCF ChIP-seq signal in GSI vs. DMSO (x-axis). Red dots are T-ALLgained sites. b ATAC-seq levels at T-ALLgained CTCF sites in Jurkat cells at DMSO, GSI treated for 72 h, and GSI washout for 16 h. *, p < 0.05, **, p < 0.001, by paired two-tailed Student’s t test. c FLAG-NOTCH1 immunopurified proteins from control and NOTCH1-FLAG-expressing CUTLL1 cells were resolved on SDS-PAGE gels and interacting partners are visualized by western blot. IgG was immunopurified as a negative control. IB, immunoblot; IP, immunoprecipitation. d, e ChIP-seq signals for BRG1 (d) and CTCF (e) surrounding constitutive (gray), AMLlost (blue), and AMLgained (red) CTCF binding sites in AML cell line EOL1. Normalized ChIP-seq read counts (RPKM) covering 2-kb regions centered at CTCF binding sites were plotted per 10-bp non-overlapped bins. f Percentage of genes in different groups that are downregulated (log2FC < − 0.26, FDR < 0.001) in shCTCF experiment in CUTLL1. Black: Genes located in the T-ALLgained-CTCF-containing chromatin domains. Red: Genes located in the T-ALLgained-CTCF-containing domains that are also upregulated (log2FC > 0.26, FDR < 0.001) in T-ALL compared to normal T cell. *, p < 0.05, **, p < 0.001, by two-tailed Fisher’s exact test. g BART-predicted TFs that target the downregulated genes (log2FC < − 0.58, FDR < 0.01) upon CTCF silencing experiments in CUTLL1. h MA plot showing differential gene expression after shCTCF treatment in CUTLL1. Most NOTCH1 target genes (red) are downregulated. i Differential gene expression between CUTLL1 and normal T cells. Group A: genes located in dynamic-NOTCH1-containing domains. Group B: genes located in domains containing both dynamic-NOTCH1 and T-ALLgained CTCF binding sites. *, p < 0.05, **, p < 0.001, by two-tailed unpaired Student’s t test