Fig. 4

Distinct heterochromatin signatures of PMDs predict replication timing. a HepG2 PMDs are classified into three classes according to replication timing signals: cluster 1 represents the early/mid S phase associated with PMD boundaries, cluster 2 represents the middle/late S phase (S3/S4), and cluster 3 represents the very late S phase (S4) and G2. b Epigenetic mark signatures across clusters in a; H3K27me3 is highly enriched in cluster 1 and in the PMD boundaries of cluster 3 and less so in cluster 2. H3K9me3 enrichment is similar in cluster 1 and cluster 2 and become more prominent in cluster 3. The elongation mark H3K36me3 is depleted in all clusters. PMDs in cluster 3 have the lowest methylation level among the other two clusters and encompass the transcriptionally inactive genes. c Different epigenomic data tracks from chr2 shown in the following order: DNA methylation profiles, H3K9me3, H3K27me3, and H3K36me3 histone marks of HepG2 and PHH, replication timing signals (G1-G2) of HepG2, clustered HepG2-hypomethylated/PMDs according to a, Hi-C contact matrices of HepG2, and liver with the corresponding called TADs, tRNA, and RefSeq genes. The highlighted region shows one long PMD, roughly 3Mb, extends over three TADs which are splitting according to H3K9me3 signal enrichment. Two of these TADs, marked in red, fuse into one TAD in the liver sample in agreement with the H3K9me3 signature