Fig. 6

Chrom3D modeling of positioning of TADs containing laminopathy-associated LMNA LADs in FPLD2 patient cells reveals disease-specific LADs in the nuclear interior. a LMNA ChIP-seq profiles (shown as log(ChIP/input) ratios; scales: –3 to 3 centered on 0) and LADs in control and FPLD2 fibroblasts. b Example of differential LMNA enrichment patterns in control and FPLD2 fibroblasts. c Overlap of control and FPLD2 LADs (in Mb). Jaccard index of overlap is 0.51. Control-specific LADs (141.2 Mb) were determined by LAD regions found in at least one control cell type and not in any of the FPLD2 fibroblasts; FPLD2-specific LADs (125.7 Mb) were determined by LAD regions found in at least one FPLD2 fibroblast type and not in any of the controls. LADs were identified as described in “Methods.” d Radial distribution of all TADs containing LADs across 100 Chrom3D structures modeled from control and FPLD2 nuclei (bars 5.6) and of TADs containing FPLD2-specific LADs (bars 1, 2) and control-specific LADs (bars 3,4), both in control nuclei (blue bars) and FPLD2 nuclei (green bars); *P < 2.2 × 10^–16 (Mann–Whitney U tests). e Radial placement of TADs containing control-specific LADs (blue beads) in a modeled control nucleus and of FPLD-specific LADs (green beads) in a modeled FPLD2 nucleus. f Fold-change expression level of genes within FPLD2-specific (“gained”) LADs in FPLD2 fibroblasts and within control-specific (“lost”) LADs in control fibroblasts; data expressed as log2(FPKM patients/FPKM controls); numbers are number of outliers; *P = 3.8 × 10^–9 (Mann–Whitney U test). g Expression levels of all genes and of genes in LMNA LADs in FPLD2 and control fibroblasts; *P < 2.2 × 10^–16 (Mann–Whitney U test)