Genome-wide profiling of 8-oxoguanine reveals its association with spatial positioning in nucleus

DNA Res. 2014 Dec;21(6):603-12. doi: 10.1093/dnares/dsu023. Epub 2014 Jul 9.


8-Oxoguanine (8-oxoG) is one of the most common DNA lesions generated by reactive oxygen species. In this study, we analysed the genome-wide distribution profile of 8-oxoG by combining immunoprecipitation by antibodies specific for the DNA fragments containing 8-oxoG with a microarray that covers rat genome. Genome-wide mapping of 8-oxoG in normal rat kidney revealed that 8-oxoG is preferentially located at gene deserts. We did not observe differences in 8-oxoG levels between groups of genes with high and low expression, possibly because of the generally low 8-oxoG levels in genic regions compared with gene deserts. The distribution of 8-oxoG and lamina-associated domains (LADs) were strongly correlated, suggesting that the spatial location of genomic DNA in the nucleus determines the susceptibility to oxidative modifications. One possible explanation for high 8-oxoG levels in LADs is that the nuclear periphery is more susceptible to the oxidative damage caused by the extra-nuclear factors. Moreover, LADs have a rather compact conformation, which may limit the recruitment of repair components to the modified bases.

Keywords: 8-oxoguanine; DNA modification; lamina-associated domain; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / chemistry
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • DNA / genetics
  • DNA / metabolism*
  • Gene Expression Regulation / genetics
  • Genome*
  • Genome-Wide Association Study
  • Guanosine / analogs & derivatives*
  • Guanosine / genetics
  • Guanosine / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism


  • Antibodies, Antinuclear
  • Reactive Oxygen Species
  • Guanosine
  • 8-hydroxyguanosine
  • DNA

Associated data

  • GEO/GSE54007