Supplementary Figure 7: Intra-TAD structural changes in EZH2^WT and EZH2^Y646X cells by interactome.

a, Hi-C contact map at 20kb resolution of the genomic region Chr.6 108.3-109.8Mb in Karpas422-EZH2^Y646N (left) and Karpas422-EZH2^Y646N treated with GSK126 for 72 hours (right). TAD boundaries are contoured in black and representative genes within the TADs are shown. b, Number of normalized paired-end reads between Chr.6 108,860-108,880 kb and Chr.6 109,380-109,400 kb in the indicated Hi-C cell lines and conditions. P-value derived by two-tailed Wilcoxon test comparing normalized read counts in EZH2^Y646X (n = 4) cell lines and in EZH2^WT or EZH2^Y646X cell lines (n = 4 in total) treated with GSK126. c, Significant interactions in WSU-DLCL2-DMSO (top) or WSU-DLCL2-GSK126 (bottom) determined by HiC-DC. Bin-pairs within a 2Mb windows were tested (see Methods). d, Significantly different interactions (q-value < 0.1) between WSU-DLCL2-DMSO and WSU-DLCL2-GSK126 (n = 435 tested interactions). Empirical q-values determined as described in Methods. e, Most significantly different interactions between WSU-DLCL2-DMSO and WSU-DLCL2-GSK126. f, UMI-4C domainogram: mean number of contacts (% of the maximum) in the Chr.6 108.80-109.45kb region in Karpas422-DMSO (top) and Karpas422-GSK126 (bottom) using Primer 2. g, Normalized number of UMI-4C reads in Karpas422-DMSO and Karpas422-GSK126 obtained with Primer 2. Normalized read-counts are binned at 5kb and averaged within a sliding 5 bin-window. h, (Top) Most significant different interactions determined by HiC-DC between Karpas422-GSK126 than Karpas422-DMSO (see Methods). Blue: stronger in Karpas422-GSK126, Red: stronger in Karpas422-DMSO. (Bottom) ChIP-seq tracks for H3K4me3 (green), H3K27Ac (dark blue), H3K4me1 (light blue), and H3K27me3 (violet) in Karpas422 and OCI-Ly7 (n = 2 ChIP-seq experiments per cell line). i, (Left) Significant interactions in Karpas422-EZH2^Y646N (top) and OCI-Ly19-EZH2^WT (bottom) determined by HiC-DC. Bin-pairs within a 2Mb windows were tested (see Methods). (Right-top) Significantly different interactions (q-value < 0.1) between Karpas422-EZH2^Y646N and OCI-Ly19-EZH2^WT (n = 435 tested interactions). Empirical q-values determined as described in Methods. (Right-bottom) Most significantly different interactions between Karpas422-EZH2^Y646N and OCI-Ly19-EZH2^WT. j, Distribution of the number of significant different interactions between Karpas422-EZH2^Y646N and OCI-Ly19-EZH2^WT cells in in 100 sets of 72 randomly sampled neutral TADs and value observed in 72 inactive TADs (red line). Empirical p-value corresponds to fraction of random sets of neutral TADs with a number of significant interactions equal or greater to the one observed in inactive TADs. k, Venn diagram of the overlap between significant different interactions between Karpas422-EZH2^Y646N and OCI-Ly19-EZH2^WT. P-value derived by two-tailed Fisher’s exact test, OR: odds ratio.