While the potential involvement of VprBP-mediated EZH2 phosphorylation in melanomagenesis was not explored in the current study, the stable depletion and inhibition of VprBP in melanoma cells expressing low levels of EZH2 still generated a substantial increase in melanomagenic gene transcription and cell growth rates, lending support to the notion that the pro-melanomagenic activity of VprBP is mainly through H2AT120p at target genes. This evidence concerns the gene EZH2 and melanoma.