Snail plays an important role in metastasis of ovarian cancer; our previous works confirmed that Snail expression correlated with the stage of ovarian cancer. In early-stage tumors, Snail was localized in both the cytoplasm and nucleus. In late stage and metastatic lesions, the level of Snail was elevated, and Snail was mainly localized in the nucleus. To further illustrate the mechanisms of Snail regulation in ovarian cancer, we performed the Reverse Phase Protein Assay (RPPA) using the SKOv3-Snail inducible cell line. RPPA analysis revealed that Dnmt1, the maintenance DNA methylation enzyme, was extremely high in Snail induced cells compared to the control. Snail-Dnmt1 correlation was validated by Western blot in SKOv3-Snail and HO8910PM-Snail inducible cells. Most interesting finding is that compare to non-induced cells, the protein level of Dnmt1 was enhanced in the cytoplasm after Snail induced, while there is no change in nucleus both in Snail-induced cells and its control. We therefore investigated whether Dnmt1 expression was associated with Snail, Dnmt1 was examined in an ovarian tissue array by immunohistochemistry, it shows that the expression of Dnmt1 was extremely higher in metastasis tumor compared with its primary tumor. Most intriguingly, we observed that Dnmt1 was mainly localized in the nucleus of primary tumors; whereas it exhibited a higher level in both nucleus and cytoplasm of metastasis lesions. All these results suggested that Snail could up-regulate Dnmt1, and sequester it in cytoplasm when metastasis occurred. As we know, sequestration of Dnmt1 in the cytoplasm may result global DNA hypomethylation. To understand the epigenetic alteration by Snail, SKOv3-Snail inducible cells were used to perform methylation array analysis. DNAs were immunoprecipitated by anti-5’-methylcytidine antibody, labeled with Cy5 or Cy3, then hybridized to NimbleGen Multiplex CpG Island Plus RefSeq Promoter Array. Chip analysis found methylation level of more then 40 genes were decreased after Snail induction, these genes were involved in cell transcription and adhesion. Further studies are going on to characterize these candidates. Our results inferred that Snail might regulate gene methylation through sequestering Dnmt1 in cytoplasm.