Fig. 4: Early chromatin structure disruption in progeria is not accompanied by alterations in H3K9me3.

a Genomic tracks for paired H3K9me3 ChIP-seq and SAMMY-seq in three control and three HGPS samples for a representative region (40 Mb region in chr4:109000000-149000000). Enrichment signals (computed using SPP) for each sample are shown (H3K9me3 ChIP-seq – light blue; blue or yellow-colored track for SAMMY-seq S4 vs S2 enrichment or depletion, respectively). Gray boxes under each SAMMY-seq track show the SAMMY-seq domains. Number of passages in each sample for SAMMY-seq and ChIP-seq: CTRL002, P20 and P19; CTRL004, P20 and P17; CTRL013, P19 and P18; HGPS167, P13 and P14; HGPS169, P12 and P12; HGPS188, P12 and P12. For ChIP-seq data, the (ChIP – input) reads distribution was computed with SPP package and we are limiting the y axis range to zero as a minimum value. b Percentage of H3K9me3 domains conserved across all three control or all three progeria samples at indicated passages (p12-19) (computed as a percent over per sample total H3K9me3 domains size). c Overlap of H3K9me3 enriched domains and SAMMY-seq domains (S4 vs S3, S4 vs S2) for control or HGPS samples (JI on y axis, number of overlapping regions on x axis). All overlaps are significant in controls (for both S4 vs S3 and S4 vs S2 SAMMY-seq domains) (upper-tail Fisher test p-value < 0.01 for all overlaps) and in HGPS169 (only for S4 vs S2 SAMMY-seq domains). d, Representative images of H3K9me3/Lamin A immunofluorescence on 3 independent control replicates and two independent HGPS replicates at indicated passages (p11-22). Scale bars: 10 μm. e Percentage of H3K9me3 foci localized within 1 μm from the nuclear periphery in distinct cell populations (see “Methods” section). Each dot shows an independent biological replicate, the horizontal black line is the median. Number of analyzed cells/total bodies/number of bodies included in 1 μm from nuclear periphery, respectively, are reported below: CTRL001p22: 242/8598/434; CTRL002p17: 649/38160/2133; CTRL004p19: 518/34434/2006; HGPS164p11: 550/32885/1317; HGPS169p11: 65/2099/93.