Genome-wide profiling of 8-oxoguanine reveals its association with spatial positioning in nucleus.
Bottom Line: 8-Oxoguanine (8-oxoG) is one of the most common DNA lesions generated by reactive oxygen species.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.
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.Show MeSH
Related in: MedlinePlus
Mentions: To analyse the distribution of 8-oxoG in terms of the three-dimensional architecture of chromosomes, we compared its distribution with the lamin B1 profile determined for the mouse cells using DamID mapping.31 There is no profile available for lamin B1 in the rat cells; however, because it has been shown that LADs do not considerably change between different cell types and species,35 we used the data for mouse embryonic fibroblasts. First, we downloaded the data of the lamin B1 profile for these fibroblasts with the coordinates on mm9 assembly and subsequently converted the coordinates to rat (rn4) using the liftOver program.36 The 8-oxoG and lamin B1 profiles showed a clear correlation (Fig. 5; Supplementary Fig. S2). For quantitative assessment of the correlation, we divided the genomic sequence into 200 kb fragments, and calculated the averaged 8-oxoG and lamin B1 values for each fragment. We adopted 200 kb as a fragment size because LADs generally span from 100 kb to 10 Mb.37 We converted the averaged values of these two indices for each 200 kb fragment into a contour plot to visually evaluate the relationship between 8-oxoG and lamin B1 profiles (Fig. 6A). We observed a positive trend between 8-oxoG and lamin B1 levels even though LADs are high AT content. The transitions between regions with low and high levels of lamin B1 are extremely sharp;37 we observed clear bimodal distribution in terms of lamin B1 levels. Next, following the bimodal distribution, the genomic fragments were grouped into two subsets using the averaged lamin B1 value of 0 as a cut-off, and the data were used to plot the histograms shown in Figure 6B. Averaged 8-oxoG values in the negative and positive lamin B1 groups were −0.13 and 0.25, respectively. The histograms show significantly different distributions (Student's t-test; P < 2.2 × 10−16), indicating that there is an excess of 8-oxoG in LADs.Figure 5.
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.