DNA methylation reprogramming in cancer: does it act by re-configuring the binding landscape of Polycomb repressive complexes?

Bioessays. 2014 Feb;36(2):134-40. doi: 10.1002/bies.201300130. Epub 2013 Nov 26.


DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer-associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible for the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis-targeting could directly drive carcinogenesis and disease progression.

Keywords: DNA methylation; H3K27me3; Polycomb; cancer epigenetics; epigenomics; reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Methylation / genetics
  • DNA Methylation / physiology*
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology
  • Humans
  • Neoplasms / genetics*
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism*


  • Polycomb-Group Proteins