Fig. 1: Genome-wide binding landscape of TOP2B in human cancer cells.

a Overview of ChIP-seq analysis. TOP2B, CTCF, and RAD21 binding sites were identified in clinical samples of human hepatocellular carcinomas. Venn diagram shows sites bound by the three factors. b Evolutionary conservation, pan-tissue activity, and functional characteristics of binding sites. TOP2B-CTCF-RAD21 sites and CTCF-RAD21 sites are highly conserved based on DNA-binding profiles of CTCF and TOP2B in mammalian livers, occur frequently at constitutively active CTCF binding sites measured from 70 human cell lines, and are enriched in sites with double strand break (DSB) activity. P-values are from one-tailed hypergeometric tests. c Chromatin states of TOP2B binding sites in normal tissue types from the Roadmap Epigenomics project (X-axis). Chromatin states of TOP2B-CTCF-RAD21 sites and TOP2B-RAD21 sites were compared to sites lacking TOP2B binding (i.e., CTCF-RAD21 sites and RAD21-only sites, respectively). Colors in the heatmap show log odds ratios and asterisks show false discovery rate (FDR)-adjusted P-values (q-values) from two-tailed hypergeometric tests (FDR < 0.05). Tissues and chromatin states are ordered by total significance (TSS, transcription start site). d Transcriptional associations of TOP2B binding sites in cancer. Violin plots show mean gene expression levels of genes adjacent to binding sites. P-values are from two-tailed Wilcoxon tests. Pie charts below show the fractions of sites at near genes. P-values are from one-tailed hypergeometric tests. Pan-cancer transcriptome data from the Pan-cancer Analysis of Whole Genomes (PCAWG) study is shown. Boxplots span interquartile range (IQR; 25–75%), lines show median values, whiskers show values within 1.5x IQR, and site counts are shown below. e Long-range chromatin interactions involving TOP2B binding sites from 27 human cell types. P-values are from two-tailed Wilcoxon tests. Source data are provided as Source Data files.