8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most common marker of oxidative stress and its accumulation within the genome has been associated with major human health issues such as cancer, aging, cardiovascular and neurodegenerative diseases. 8-oxodG is considered the main source of dC:dG to dA:dT transversion. The majority of 8-oxodG is preferentially repaired by OGG1 glycosylase/AP (apurinic/apyrimidinic) lyase-initiated BER (Base Excision Repair) pathway.
It has been widely demonstrated that the 8-oxodG accumulation in the promoter regions of specific genes can stimulate transcription via the BER pathway. Based on this knowledge, we wondered whether the oxidative DNA damage could globally be correlated with the transcription process. Here, we report the genome-wide distribution of 8-oxodG in human non- tumorigenic epithelial breast cells (MCF10A) using OxiDIP-Seq which combines the immunoprecipitation anti–8-oxodG antibodies with high- throughput sequencing. We show a specific 8-oxodG bimodal distribution within promoter regions and identify a subset of human promoters that accumulate 8-oxodG under steady-state condition. Furthermore, the comparison between OxiDIP-Seq and ChIP-Seq of Ser5- and Ser2- phosphorylated isoforms of RNA Polymerase II or GRO-Seq strongly suggest the association between 8-oxodG accumulation and transcription process. Besides, by performing OxiDIP-seq in quiescent (G0) cells, we classified the oxidized promoters in two subsets. The growing-specific promoters accumulate 8-oxodG through DNA replication-dependent events while the persistently oxidized promoters accumulate 8-oxodG through replication-independent and transcription- associated events
