Fig. 6: MAD mutation associates with loss of chromatin compartmentalization and increase in TADs.

a Normalized heatmap of specific region (q arm of chromosome 1) in WT and MAD-MSCs. The color maps of relative interaction probability in WT-MSCs and MAD-MSCs were displayed on the same scale. The A and B compartments were defined by PC1 signal (positive PC1 regions in red color represent A compartments, negative PC1 regions in blue color represent B compartments). b Statistical analysis of compartment interaction between compartment A and compartment B in WT-MSCs and MAD-MSCs according to Saddle plot analysis. c Analysis of the lamina-compartment interactions. d Boxplot showing length of WT TADs (n = 3823) and MAD TADs (n = 4001), with 2 biological replicates for Hi-C. Box plots display the median as the center line, the 25th and 75th percentiles as the bounds of the box, and the whiskers represent the minimum and maximum values within 1.5 times the interquartile range from the lower and upper quartiles. All p-values were determined using the two-sided Wilcoxon rank-sum test. e Overall view of TAD number in WT-MSCs and MAD-MSCs. f Category of differential TADs number presented in MAD-MSCs, including stable, shortened, shifted without change in length, and enlarged. g Overall view of CTCF redistribution in MAD-MSCs. h The distribution of CTCF across lamin-chromatin interaction sites. i Overall view of altered chromatin features, including CTCF binding, ATAC, H3K27ac, H3K27me3, H3K9me3, and gene expression in TADs. All p-values were determined using the two-sided Wilcoxon rank-sum test. j Integrative analysis of TAD disorganization and chromatin features in genomic region covering a dysregulated aging-associated gene, SETDB2, in MAD-MSCs. k Cross-analysis of the enrichment of dysregulated genes resulted from shortened TADs in MAD-MSCs with geroprotection/senescence-associated profile in hMSCs aging models. Color depth indicates enrichment score.