Extended Data Figure 7: Methylation dynamics in mouse T cells and in human tissues.

a, Pattern clusters for low methylation loci, using one non-clonal and two clonal CD8⁺ T-cell populations. Persistent and high noise clusters (III) are identified. b, Annotation of pattern clusters in a, showing enrichment of H3K27me3 loci at the persistent classes. c, Pattern clusters for high methylation loci. d, Pattern clusters for intermediate methylation loci. e, Distribution of replication time (using ENCODE Repli-chip data on MEL cells, quantile normalized), on loci classified according to a–d. As observed for WI38 cells, persistent and intermediate methylation loci tend to be observed at late replicating domains. f, Comparison of human ES-cell average methylation and methylation in three different human tissues, stratified according to ES-cell time of replication (late replicated, left; early replicated, right). These data show that methylation in adult tissues is massively degraded compared to ES cells, in a replication-time-dependent fashion, as also predicted by our clonal analysis. g, Shown are average epipolymorphism values for loci that show high methylation in human ES cells (>0.9) and lose methylation in adult tissues (x-axis). This analysis shows that methylation loss in adult tissues is correlated with extremely high heterogeneity, suggesting that the stochastic dynamics we observed in in vitro clonal populations widely affect methylation in vivo.