Figure 7.

A model for de-repression of Polycomb target genes upon loss of DNA methylation. In normal cells, PRC2 is targeted to chromatin in a process that involves unmethylated stretches of DNA, such as CpG islands (PRC2 targeting is indicated by green arrows). DNA methylation has a negative effect on PRC2 binding to chromatin and so constrains PRC2 targeting. When global DNA methylation levels are reduced, PRC2 binding and H3K27me3 increase at numerous additional genomic loci leading to a dilution of available PRC2 from its normal targets. Note that only loci that are somehow permissive to PRC2 binding show increased H3K27me3 in hypomethylated cells. Reduced PRC2 binding to its normal target promoters results in loss of transcriptional repression. PRC2, Polycomb Repressive Complex 2.