title: 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.
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Yoshihara
authors.affiliation: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Akatsuka
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan Japan Science and Technology Agency, CREST, Fukuoka 812-8582, Japan mikita@bioreg.kyushu-u.ac.jp toyokuni@med.nagoya-u.ac.jp.
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
authors.affiliation: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan mikita@bioreg.kyushu-u.ac.jp toyokuni@med.nagoya-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000737:chemistry; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D016678:Genome; D055106:Genome-Wide Association Study; D006151:Guanosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D017382:Reactive Oxygen Species; D006151:Guanosine; C046215:8-hydroxyguanosine; D004247:DNA
keywords: 8-oxoguanine; DNA modification; lamina-associated domain; oxidative stress