Base-Resolution Analysis of 5-Hydroxymethylcytosine by One-Pot Bisulfite-Free Chemical Conversion with Peroxotungstate

J Am Chem Soc. 2016 Nov 2;138(43):14178-14181. doi: 10.1021/jacs.6b06428. Epub 2016 Oct 24.

Abstract

5-Hydroxymethylcytosine (hmC) is an essential intermediate in the active DNA demethylation pathway. Here we report a new base-resolution method for measuring hmC by combining peroxotungstate-mediated oxidation and sequencing analysis. We reveal that an oxidized product of hmC, trihydroxylated thymine (thT), tolerated the incorporation of dATP as a substrate in the process of DNA polymerase elongation. By comparing the results of Sanger sequencing before and after the oxidation, we observed that hmC sites on single-stranded DNAs could be discriminated from unmethylated cytosines. We found that a thermal cycle condition during peroxotungstate treatment enhanced the oxidation reaction of hmC in double-stranded DNA. Furthermore, Illumina sequencing analysis of hmC-containing synthetic genome fragments enabled us to identify simultaneously the positions of hmC in base resolution. This bisulfite-free simple hmC detection technique could facilitate the acquisition of epigenomic information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives*
  • 5-Methylcytosine / chemistry
  • Base Pairing
  • Base Sequence
  • DNA / chemistry
  • DNA / genetics
  • Selenium Radioisotopes
  • Sulfites / chemistry
  • Tungsten Compounds / chemistry*

Substances

  • Selenium Radioisotopes
  • Sulfites
  • Tungsten Compounds
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • bis(N,N,N-trimethylamino)ethylselenide-Se iodide
  • DNA
  • hydrogen sulfite
  • tungstate