modulate gene expression. Chromodomain helicase DNA-binding protein 4 (CHD4), a component of the (NuRD) complex, is recruited by OGG1 to oxidative DNA damage sites. CHD4 then attracts DNA and histone methylating enzymes that repress transcription of associated genes. Seifermann and Epe noted that the highly selective induction of 8-oxo-dG in the promoter sequences observed in transcription induction may be difficult to explain as a consequence of general oxidative stress. However, there appears to be a mechanism for site-directed generation of oxidized bases in promoter regions. Perillo et al., showed that the lysine-specific histone demethylase LSD1 generates a local burst of reactive oxygen species (ROS) that induces oxidation of nearby nucleotides when carrying out its function. As a specific example, after treatment of cells with an estrogen, LSD1 produced H2O2 as a by-product of its enzymatic activity. The oxidation of DNA by LSD1 in the course of the demethylation of histone H3 at lysine 9 was shown to be required for the recruitment of OGG1 and also topoisomerase IIβ to the promoter region of bcl-2, an estrogen-responsive gene, and subsequent transcription initiation. 8-oxo-dG does not occur randomly in the genome. In mouse embryonic fibroblasts, a 2 to 5-fold enrichment of 8-oxo-dG was found in genetic control regions, including promoters, 5'-untranslated regions and 3'-untranslated regions compared to 8-oxo-dG levels found in gene bodies and in intergenic regions. In rat pulmonary artery endothelial cells, when 22,414 protein-coding genes were examined for locations of 8-oxo-dG, the majority of 8-oxo-dGs (when present) were found in promoter regions rather than within gene bodies. Among hundreds of genes whose expression levels were affected by hypoxia, those with newly acquired promoter 8-oxo-dGs were upregulated, and those genes whose promoters lost 8-oxo-dGs were almost all downregulated. Positive role of 8-oxo-dG in memory Oxidation of guanine, particularly within CpG sites, may be especially important in learning and memory. Methylation of cytosines occurs at 60–90% of CpG sites depending on the tissue type. In the mammalian brain, ~62% of CpGs are methylated. Methylation of CpG sites tends to stably silence genes. More than 500 of these CpG sites are de-methylated in neuron DNA during memory formation and memory consolidation in the hippocampus and cingulate cortex regions of the brain. As indicated below, the first step in de-methylation of methylated cytosine at a CpG site is oxidation of the guanine to form 8-oxo-dG. Role of oxidized guanine in DNA de-methylation The first