Figure 4. Reprogramming of DNA methylation during cancer progression.

The transition from normal to cancerous state is associated with changes in genome‐wide patterns of DNA methylation. While promoter CpG islands of active genes marked by H3K4me3 remain free of DNA methylation, polycomb‐regulated promoter CpG islands become hypermethylated, possibly due to aberrant targeting of DNMT3A/B through an unknown mechanism. The gene‐poor, H3K9 methylation‐rich, late‐replicating lamina‐associated domains undergo progressive loss of maintenance methylation during cancer cell replication. Gene body and intergenic regions marked by H3K36 methylation are protected from such mitotically linked DNA hypomethylation, presumably due to the preferential targeting and activity of de novo methyltransferases DNMT3A/B.