Local contact alterations during senescence. (A) The proportions of overlapped TAD boundaries between four cell states. (B) Scatterplot of the numbers of increased and decreased interactions (FDR < 0.01) for each TAD. Each point represents a TAD; x and y coordinates represent the numbers of increased and decreased interactions within the same TADs. Based on two numbers, TADs were classified into three types—increased-, decreased-, and unchanged-interactions TADs. (C) Box plots of the enrichment of histone modifications of G for the three TAD types. A Wilcoxon test was used for calculating P-values. (D) Box plots of fold changes of gene expression between DS and G. Genes whose maximum FPKM of G and DS > 1 were used. P-values were calculated by t-test. (E) Scatterplot of the ATAC-seq peak numbers in G and DS for the three TAD types. TADs are the units for counting ATAC-seq peaks. The mean ratios of DS to G for peak numbers are 1.08, 1.16, and 1.83, corresponding to decreased-, unchanged-, and increased-interaction TADs, respectively. Wilcoxon test, P = 4.00 × 10−298 for increased versus decreased; P = 6.11 × 10−271 for increased versus unchanged. (F) Scatterplot of H3K9me3 pileup in G and DS. Each point represents a 10-kbp bin and color represents the types of TADs to which it belongs. Increased-interaction TADs are enriched for relative decreased H3K9me3 than the two other TAD types. (G) Scatterplot of H3K27me3 pileup in G and DS. Increased-interaction TADs are enriched for relative increased H3K27me3, whereas decreased-interaction TADs are enriched for relative decreased H3K27me3. (H,I) WashU Epigenome Browser views of two examples of increased- and decreased-interaction TADs. Boxes in panel H shows increased interactions within TADs, which are enriched for H3K9me3 of G and novel ATAC-seq peaks in DS. The regions were also accompanied by decreased H3K9me3 and increased H3K27me3 during senescence. Panel I shows two decreased-interaction TADs showing opposite features.
