Functions of DNA methylation: islands, start sites, gene bodies and beyond

Nat Rev Genet. 2012 May 29;13(7):484-92. doi: 10.1038/nrg3230.


DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • CpG Islands / genetics*
  • CpG Islands / physiology
  • DNA Methylation / genetics*
  • DNA Methylation / physiology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Genes / genetics*
  • Genes / physiology
  • Models, Molecular
  • Regulatory Elements, Transcriptional / genetics*
  • Regulatory Elements, Transcriptional / physiology
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Repetitive Sequences, Nucleic Acid / physiology
  • Transcription Initiation Site / physiology*