a, Normalized enrichment of lamin A/C ChIP–seq signals, histone markers (H3K4me3 and H3K27me3) and ATAC-seq signals within ±0.4 Mb of mapped LAD borders. The genomic locations of LADs were obtained from ChIP–seq on lamin A/C using two different antibodies (Abcam 8984, blue line, sc-376248, green line) in control iPSC-CMs (III-3). b, Representative images of ChIP–seq, ATAC-seq and RNA-seq of chromosome 12 (133 Mb). The red box shows LADs explicitly called in mutant iPSC-CMs (gain); the purple box shows LADs called in both control and mutant iPSC-CMs (overlapping); the blue box shows LADs explicitly called in control iPSC-CMs (loss). c–e, Number (c), genomic coverage (d) and mean of length of LADs (e) in control, mutant, gain, overlapping and loss LADs. ChIP–seq on lamin A/C (Abcam 8984) was used for data analysis. f, g, Average peak intensity of H3K4me3 and H3K27me3 of each LAD. n = 184 (loss), n = 370 (overlapping), n = 184 (gain) for H3K4me3; n = 273 (loss), n = 504 (overlapping), n = 273 (gain) for H3K27me3. Data are mean and minimum to maximum; Wilcoxon matched-pairs signed-rank test was used to calculate P values. h, Scatter plot of normalized lamin A/C, ATAC and histone marker (H3K4me3 and H3K27me3) enrichment of each LAD. The y axis shows the log 2 -transformed relative normalized lamin A/C enrichment of each LAD in mutant iPSC-CMs compared to control iPSC-CMs. The x axis shows the log 2 -transformed relative normalized ATAC and histone marks enrichment of each LAD in mutant iPSC-CMs compared with control iPSC-CMs. Each data point represents one LAD. The statistical significance was obtained using one-way ANOVA; n = 587 for sc-376248 and n = 585 for Abcam 8984. i, Percentage of differentially expressed genes in mutant iPSC-CMs compared to control iPSC-CMs. j, Number of differentially expressed genes located in mutant iPSC-CMs compared to control iPSC-CMs. (FDR-adjusted P < 0.01; log 2 -transformed fold change in expression of >1 or <−1). k, Distribution of log 2 -transformed fold change in FPKM in control and mutant iPSC-CMs. A non-parametric Kruskal–Wallis (testing for two-sided differences) followed by Dunn’s post hoc test was used to adjust for multiple comparisons; n = 266 (gain), n = 8171 (non-LADs), n = 835 (overlapping), n = 206 (loss).