Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development

Cancer Metastasis Rev. 2008 Jun;27(2):315-34. doi: 10.1007/s10555-008-9118-y.

Abstract

Cancer cells and tissues exhibit genome wide hypomethylation and regional hypermethylation. CpG-methylation of DNA ((Me)CpG-DNA) is defined as the formation of a C-C covalent bond between the 5'-C of cytosine and the -CH(3) group of S-adenosylmethionine. Removal of the sole -CH(3) group from the methylated cytosine of DNA is one of the many ways of DNA-demethylation, which contributes to activation of transcription. The mechanism of demethylation, the candidate enzyme(s) exhibiting direct demethylase activity and associated cofactors are not firmly established. Genome-wide hypomethylation can be obtained in several ways by inactivation of DNMT enzyme activity, including covalent trapping of DNMT by cytosine base analogues. Removal of methyl layer could also be occurred by excision of the 5-methyl cytosine base by DNA glycosylases. The importance of truly chemically defined direct demethylation of intact DNA in regulation of gene expression, development, cell differentiation and transformation are discussed in this contribution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Gene Expression Regulation*
  • Humans
  • Neoplasms / genetics*
  • Transcription, Genetic*

Substances

  • DNA (Cytosine-5-)-Methyltransferases