The impact of metabolism on DNA methylation

Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R139-47. doi: 10.1093/hmg/ddi100.


Methylation of genomic cytosines is one of the best characterized epigenetic mechanisms, and investigation of its relationship with other biochemical pathways represents a critical stage in the elucidation of biological information processing. The field also has immense potential for the development of medical treatments for any number of conditions ranging from aging to neurological disorders. The DNA methylation status of genes is responsible for many heritable traits and varies more or less independently of the genetic code. This variation is often a result of cellular environmental factors including metabolism. A key metabolite in this regard is homocysteine. Knowledge of homocysteine metabolism continues to be amassed, yet the part played by aberrant DNA methylation in homocysteine-related pathologies is often, at best, conjectural. In this analysis, we will review recent insights and attempt to speculate meaningfully concerning the dynamics of the methionine cycle in relation to DNA methylation and disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Arteriosclerosis / metabolism
  • DNA Methylation*
  • Folic Acid / metabolism
  • Gene Expression Regulation*
  • Glycine N-Methyltransferase
  • Homocysteine / metabolism*
  • Humans
  • Methionine / metabolism*
  • Methyltransferases / metabolism
  • Models, Biological
  • S-Adenosylmethionine / metabolism


  • Homocysteine
  • S-Adenosylmethionine
  • Folic Acid
  • Methionine
  • Methyltransferases
  • Glycine N-Methyltransferase