Methylation differences at the +12 CpG site found in this study may have several effects. The +12 CpG site is located in a Sp1 transcription binding site. In general, methylation of CpG sites in promoter regions decreases gene expression. In studies of Sp1 transactivation of genes with methylated and unmethylated Sp1 transcription binding sites, most studies show decreased binding of Sp1 to its cognate binding site (Alikhani-Koopaei et al. 2004; Douet et al. 2007; Iguchi-Ariga and Schaffner 1989); however, an increase in affinity for Sp1 with methylated DNA has also been observed (Jane et al. 1993). Methylation of Sp1 transcription binding sites has been shown to decrease Sp1 transactivation (Douet et al. 2007; Iguchi-Ariga and Schaffner 1989); however, increases in gene expression have also been reported (Cheng et al. 2005).
