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
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Mentions: After the negative relationship between 8-oxoG distribution and gene density had been established by visual inspection of the distribution profiles and chromosome-scale quantification, we performed quantitative assessment of these relationships at a higher resolution over the entire genome. To achieve this, we divided the chromosomes into non-overlapping 1 Mb fragments, and counted the genes and averaged log2(IP/input) value of 8-oxoG for each fragment (Fig. 4). The box plot clearly shows that 8-oxoG levels increase with the decrease in the number of genes in a fragment (Pearson's correlation coefficient (r) = −0.47, P < 0.001), particularly for fragments with less than three genes. For the fragments without any genes (627 fragments), the median of averaged log2(IP/input) value of 8-oxoG is 0.39, while for the fragments with three genes (255 fragments), the averaged log2(IP/input) value for 8-oxoG level is −0.11. There are no clear differences between the values for 8-oxoG levels for the fragments with eight or more genes. This shows that the fragments with two or fewer genes tend to have more 8-oxoG than the fragments with three or more genes, confirming that the observed negative relationship between the profile for 8-oxoG levels and gene density was true on the genome-wide scale. In general, the GC content in gene deserts are lower than that in gene-rich regions, indicating that higher 8-oxoG levels in gene deserts are not simply due to biased base composition.Figure 4.
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.