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


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.

SUBMITTER: Yoshihara M 

PROVIDER: S-EPMC4263294 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Yoshihara Minako M   Jiang Li L   Akatsuka Shinya S   Suyama Mikita M   Toyokuni Shinya S  

DNA research : an international journal for rapid publication of reports on genes and genomes 20140709 6


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 wit  ...[more]

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