Figure 6. A schematic model of gene activation mechanism through 8-OHdG modification at methylated CpG locus upstream of TATA-box.

When the CpG locus is not methylated, TBP gains access to TATA-box and transactivates the gene. (B) By the addition of single methylation at the CpG locus, the sequence becomes the target of MeCP2. As a result, TBP binding to TATA-box is disturbed, and the gene becomes inactive. (C) Guanine modification by oxidative stress typically results in the induction of hydroxylation at position 8, which sequesters MeCP2 binding to the target DNA. (D) As a consequence, TBP binding to TATA-box is restored, and the gene is reactivated.