Genome-wide analysis of 8-oxoguanine DNA glycosylase-1 after oxidative stress exposure

We report the application of ChIP-Sequencing for profiling genome-wide distribution of 8-oxoguanine DNA glycosylase1 (OGG1, a DNA base excision repair protein), after oxidative stress exposure mediated by glucose oxidase (GOx) of cells. By obtaining an average of over 18 million of total reads per sample and over 19.5 million of unique reads per sample from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HEK293 cells. We performed gene ontology and functional pathway analysis of genes associated with peaks to identify regions of the genomes (e.g. promoter, introns, etc) where the peaks tend to occur. The results show that OGG1 is primarily associated with promoter regions in vicinity of transcription factor binding sites 5' of transcription start sites (TSS). This pattern of distribution occurs in spite of genome-wide oxidative modifications of guanines (primarily 8-oxoG). OGG1 increased significantly at regulatory regions of CXC-, CC- chemokines, cytokines and growth factors. In controls, the DNA was chromatin immunoprecipitated using antibody to NF-κB/RelA. As expected NF-κB was enriched on gene regulatory regions including those of proinflammatory,cell proliferation ones. These and other data derived from further analysis, suggest that OGG1 modulates gene expression in coordination with NF-κB.