Fig. 5: Adriamycin induces genome-wide 3D chromatin conformational change.

a Hi-C heatmaps binned at 10 kb show chromatin interactions patterns of representative regions on Chromosome 1 in control and adriamycin-treated U2OS cells. Multiple TADs and loops are diminished in adriamycin-treated cells. Prob. probability. b P(s) curves indicate relationships between chromatin contact probability and genomic distances for chromatin interactions on autosomes in control and adriamycin-treated cells. c Box plots quantify the insulation scores and boundary strength for TAD boundaries in control (ctrl) and adriamycin (adria)-treated cells. Boxes, middle 50% of TAD boundary strength. Center bars, medians of boundary strength. Whiskers, 1.5× interquartile range. p values are calculated from one-tailed Mann–Whitney U-test. n = 2 replicates (independently cultured cells were harvested, processed and sequenced separately) for each condition. d Venn diagram depicts the overlap between TAD boundaries identified in control (red) and adriamycin-treated (blue) cells. e Averaged insulation profiles in control (red) and adriamycin-treated (blue) cells for 1 Mb genomic regions centered at the 10 kb genomic bins containing control-specific (left), shared (middle), or adria-specific TAD boundaries (right). f Insulation profiles for a representative genomic region in control (red) and adriamycin-treated (blue) cells. Bars below insulation profiles indicate control-specific (red), shared (black), or adria-specific (blue) TAD boundaries identified in this region. g–i An example region (g) and overall statistic (h) demonstrated the switch of compartment A/B upon adriamycin treatment. i The change of contact frequencies between compartments upon adriamycin treatment. Genomic regions belong to the B compartment (B–B) exhibited a notable increase. j, k Relationship between gene expression and genomic A/B compartments. j Left, the boxplots showing E1 scores of all differentially expressed genes. Boxes, middle 50% of E1 scores. Center bars, medians of E1. Whiskers, 1.5× of inter-quartile range. Right, KEGG analysis of the pathways enriched in down-regulated genes with decreased E1. p values were calculated by two-sided Wilcoxon test. n = 2 technical replicates for each condition. Examples were showed in (k). l Histone modification-based learning and annotation of compositions of A/B compartments in U2OS cells performed by ChromHMM analysis (see “Methods” for the detail). The correlations between compartment switches and different chromatin states were analyzed and shown in the heatmap (right).