Snail and Slug play critical roles in the epithelial to mesenchymal transition (EMT), the mesenchymal to epithelial transition (MET) and in the maintenance of mesenchymal morphology. In this research, we investigated the correlation of DNA methylation with the transcriptional level of these two genes during the EMT/MET process. First, we used several cell lines associated with EMT/MET processes of induced pluripotent stem cell generation and differentiation, trophoblast invasion, as well as cancer progression to examine the association between DNA methylation and transcription levels of these two genes. We found an inverse correlation between DNA methylation of first intron regions and transcription levels of Snail and Slug genes in these EMT/METs. To further verify the results, we treated two trophoblast cell line BeWo and HTR8/SVneo and one induced pluripotent stem cell line with 5-aza-2'-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferase, which caused increased expression of these two genes. Lastly, we cloned the promoters of both Snail and Slug into pGL3-Basic vector, after in vitro DNA methylation and transfection into IMR90 and HTR8/SVneo cells; we observed the significant reduction of their promoter activity due to DNA methylation. In summary, based on these results, DNA methylation is one of the molecular mechanisms regulating Snail and Slug genes during EMT/MET process.
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