Here, using this murine melanoma model [26, 27], we demonstrate that Dnmt3a and Dnmt3b are downregulated in nonmetastatic (4C3−) and metastatic (4C3+) melanoma cell lines, concomitant with the overexpression of miR-29b and miR-29c, which are known Dnmt3a and Dnmt3b regulators [30]. miR-26a, which targets Ezh2 [31], a histone methyltransferase belonging to the Polycomb family, was found to be downregulated in a nonmetastatic melanoma cell line (4C3−) but upregulated in 4C3+. Here, PRDM9 is linked to melanoma.