A novel method for the efficient and selective identification of 5-hydroxymethylcytosine in genomic DNA

Nucleic Acids Res. 2011 Apr;39(8):e55. doi: 10.1093/nar/gkr051. Epub 2011 Feb 7.

Abstract

Recently, 5-hydroxymethylcytosine (5hmC) was identified in mammalian genomic DNA. The biological role of this modification remains unclear; however, identifying the genomic location of this modified base will assist in elucidating its function. We describe a method for the rapid and inexpensive identification of genomic regions containing 5hmC. This method involves the selective glucosylation of 5hmC residues by the β-glucosyltransferase from T4 bacteriophage creating β-glucosyl-5-hydroxymethylcytosine (β-glu-5hmC). The β-glu-5hmC modification provides a target that can be efficiently and selectively pulled down by J-binding protein 1 coupled to magnetic beads. DNA that is precipitated is suitable for analysis by quantitative PCR, microarray or sequencing. Furthermore, we demonstrate that the J-binding protein 1 pull down assay identifies 5hmC at the promoters of developmentally regulated genes in human embryonic stem cells. The method described here will allow for a greater understanding of the temporal and spatial effects that 5hmC may have on epigenetic regulation at the single gene level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • Carrier Proteins
  • Cytosine / analogs & derivatives*
  • Cytosine / analysis
  • Cytosine / metabolism
  • DNA / chemistry*
  • DNA / isolation & purification
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation
  • Genome, Human
  • Genomics / methods*
  • Glucosyltransferases / metabolism
  • Humans
  • Promoter Regions, Genetic
  • Protozoan Proteins

Substances

  • Carrier Proteins
  • Protozoan Proteins
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine
  • DNA
  • Glucosyltransferases