be fully explained. Interestingly, MBD2 increased gene expression in those instances where promoter demethylation occurred, suggesting that not all promoters respond in the same orderly manner. Indeed, the same is true for DNA methylation, which impedes the DNA binding of most, but not all transcription factors; SP1 binds to methylated DNA. Antisense knock down of MBD2 resulted in inhibition of active demethylation induced by valproate and caused hypermethylation and silencing of the prometastatic gene uPA in metastatic breast cancer cells. Another group reported that ectopic expression of MBD2/demethylase in hepatocyte cell line caused demethylation and activation of the hexokinase type 2 gene.125 Additional support for the demethylase activity of MBD2/demethylase emerges from the finding that expression of MBD2/demethylase is correlated with demethylation within the promoters of C-ERBB-2 and SURVIVIN genes in ovarian cancers126,127 and hypomethylated CMYC in gastric cancer.128 In addition, the Drosophila homolog of MBD2, dMBD2/3, formed foci that associated with DNA at the cellular blastoderm stage, concurrent with the activation of the embryonic genome, and also associated with the active Y chromosome.129
