Epigenetic changes during reprogramming in genes containing CpG islands. Pluripotency and developmental genes have high CpG content and suffer dramatic changes during reprogramming. The reprogramming factors (OSKM, Oct4, Sox2, Klf4, and c-Myc) target preferentially the permissive enhancers of Polycomb target genes that are devoid of DNA methylation. These include silent developmental genes and perhaps pluripotency genes that respond early to the transfactors. As a result these genes gain H3K4 methylation at proximal promoters and are primed to become poised (developmental genes) or active (pluripotency genes) at latter stages. The products of early pluripotency (EP) genes might contribute to activate, together with the transfactors, late pluripotency genes marked with DNA methylation, such as Oct4. Finally, developmental genes become poised by gain of H3K27 methylation. Permissive enhancers are represented as dotted lines. Red flags denote H3K27me3. Green flags denote H3K4me1 (one flag), H3K4me2 (two flags), and H3K4me3 (three flags). Circles correspond to unmethylated (open) or methylated (filled) CpG islands.
