Fig. 3

Gained/lost CTCF binding events associate with differential gene expression in cancer. a CTCF ChIP-seq signals (x-axis) and gene expression levels (y-axis) for one CTCF site-gene pair in 54 cell types with matched data available. R² is calculated as the association score. Sqrt, Square root; TPM, transcript count per million reads; RPKM, read count per kilobases per million reads. b Schematic of categories of intra-chromatin-domain and inter-chromatin-domain gene-CTCF pairs. c Distribution of highly correlated CTCF-gene pairs (defined as R² > 0.25) as a function of the distance between the CTCF binding site and the gene’s TSS. Pairs located within the same CTCF domain (intra-domain, blue) and across different CTCF domains (inter-domain, gray) are plotted separately. P values were obtained using two-tailed Fisher’s exact test. Dashed line represents P = 0.01. d, e Top: Percentage of highly correlated CTCF-gene pairs in which the gene sits within the same domain as a cancer-specific lost (d) or gained (e) binding site, with constitutive sites as control. “Promoter” refers to genes whose promoter region (TSS ± 2 kb) contains a CTCF binding site from a certain category. “Promoter ctrl” refers to genes whose promoter region contains a constitutive CTCF binding site as the control for cancer-specific gained/lost sites. “Intra-domain” refers to genes whose chromatin domain contains a CTCF binding site. “Domain ctrl” refers to genes whose chromatin domain contains a constitutive CTCF site as the control for those with cancer-specific gained/lost sites. Bottom: Percentage of differentially expressed genes (|log2FC| > 1, FDR < 1e−5) contained within the corresponding group of either Promoter or Intra-domain highly correlated CTCF-gene pairs in the corresponding cancer type. *, p < 0.05, **, p < 0.001, by two-tailed Fisher’s exact test. f, g Percentage of genes that are upregulated (top, log2FC > 1, FDR < 1e−5) or downregulated (bottom, log2FC < − 1, FDR < 1e−5) located in the chromatin domains containing certain group of lost (f) or gained (g) CTCF sites. *, p < 0.05, **, p < 0.001, by two-tailed Fisher’s exact test