PcG repression programs that shape beta-cell identity. Schematic illustrating how PcG-dependent modifications are placed or removed in a highly context-dependent manner during beta-cell differentiation. (A) A subset of H3K27me3+ genes in beta-cells have acquired this mark by the pancreatic endoderm progenitor stage, which is then epigenetically inherited in their cellular progeny. (B) Another subset of genes undergoes de novo H3K27me3 repression during late differentiation. These often lack CpG islands and are highly cell-type-specific H3K27me3 events. In some of these genes, repression is essential for the differentiated function of beta-cells. (C) The selective loss of PcG repression after the pancreatic progenitor stage in a core set of developmental regulators enables a convergence of transcriptional profiles in beta-cells with neuroectoderm-derived tissues.