The Mechanisms of Generation, Recognition, and Erasure of DNA 5-Methylcytosine and Thymine Oxidations

J Biol Chem. 2015 Aug 21;290(34):20723-20733. doi: 10.1074/jbc.R115.656884. Epub 2015 Jul 7.

Abstract

One of the most fundamental questions in the control of gene expression in mammals is how the patterns of epigenetic modifications of DNA are generated, recognized, and erased. This includes covalent cytosine methylation of DNA and its associated oxidation states. An array of AdoMet-dependent methyltransferases, Fe(II)- and α-ketoglutarate-dependent dioxygenases, base excision glycosylases, and sequence-specific transcription factors is responsible for changing, maintaining, and interpreting the modification status of specific regions of chromatin. This review focuses on recent developments in characterizing the functional and structural links between the modification status of two DNA bases 5-methylcytosine and thymine (5-methyluracil).

Keywords: DNA 5mC oxidation; DNA demethylation; DNA enzyme; DNA methylation; DNA methyltransferase; DNA-binding protein; DNA-protein interaction; Tet dioxygenases; base excision DNA glycosylases; modification-dependent and sequence-specific transcription factors; transcription factor.

Publication types

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

MeSH terms

  • 5-Methylcytosine / metabolism*
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism*
  • DNA Methylation
  • DNA Repair
  • Dioxygenases / chemistry
  • Dioxygenases / genetics
  • Dioxygenases / metabolism*
  • Epigenesis, Genetic
  • Gene Expression
  • Humans
  • Iron / metabolism
  • Ketoglutaric Acids / metabolism
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Processing, Post-Translational*
  • Thymine / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Ketoglutaric Acids
  • Transcription Factors
  • 5-Methylcytosine
  • Iron
  • Dioxygenases
  • Methyltransferases
  • S-adenosylmethionine-dependent phosphate methyltransferase
  • DNA Glycosylases
  • Thymine

Associated data

  • PDB/3C2I
  • PDB/4F6M
  • PDB/4F6N
  • PDB/4GZN
  • PDB/4LT5
  • PDB/4NM6