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

Minako Yoshihara, Li Jiang, Shinya Akatsuka, Mikita Suyama, Shinya Toyokuni

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    29 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)603-612
    Number of pages10
    JournalDNA Research
    Volume21
    Issue number6
    DOIs
    Publication statusPublished - Dec 1 2014

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    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Genetics

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