Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks
Figure 4.Senescence-associated DNA-methylation changes correlate with repressive histone marks. DNA-methylation profiles of MSC were compared with datasets for H3K4me3 and H3K27me3 in human ESC  (indicated in blue); H3K4me3, H3K9me3 and H3K27me3 in human MSC-AT  (red) and targets of the Enhancer of Zeste Homolog 2 (EZH2) in human MSC-BM  (orange). The overall DNA-methylation level of all 27,578 CpG sites on the microarray was much lower in comparison to the 517 senescence-associated (SA) CpG sites and to those which have been assigned for H3K27me3, H3K9me3 and targets of EZH2 (A; Box plots represent the 25th and 75th percentile for each subset and whiskers show the 5% and 95% percentiles). Notably, the 517 senescence-associated DNA-methylation changes were significantly enriched in regions with H3K27me3, H3K9me3 and EZH2 targets (B). The graphic illustrates that repressive histone marks are associated with higher levels of DNA-methylation and that senescence-associated modifications are enriched in these regions (C).