The beta-cell H3K27me3 enrichment signature includes pancreatic endoderm and terminal differentiation methylation programs. (A) In 59% of the 1480 genes that are H3K27me3+ in beta-cells, the methylation is acquired de novo, either before the pancreatic progenitor stage or during subsequent differentiation. De novo events occurring during later stages of differentiation preferentially target genes that lack CpG islands. On the other hand, in 67% of genes with H3K27me3 enrichment in beta-cells, this mark is present in progenitors and is then maintained. The cluster diagram depicts H3K27me3 enrichment (in red) in the different stages, and the presence of CpG islands is indicated in black in the adjacent column. (B) The gene profile that is H3K27me3+ in beta-cells is most similar to that of acinar, pancreatic progenitors, and liver. This was determined by Euclidean distances of genome-wide H3K27me3 distributions, as described in Methods. Similar results were observed using principal component analysis (Supplemental Fig. S6b).
