 This map showed that three of the regions (at approximately – 1000, – 3000, and – 4000) were frequently methylated, but the cytosines near the transcription start site were unmethylated.Methylation has been shown to functionally impact Sp1 sites as well as a CREB binding site.It has been shown that the CREB site must be intact for normal promoter activity to occur and methylation at the Sp1 sites may affect promoter activity.