Lysine Methyltransferase NSD1 and Cancers: Any Role in Melanoma?

SIMPLE SUMMARY: Epigenetic events, which comprise post-translational modifications of histone tails or DNA methylation, control gene expression by altering chromatin structure without change in the DNA sequence. Histone tails modifications are driven by specific cellular enzymes such as histone methyltransferases or histone acetylases, which play a key role in regulating diverse biological processes. Their alteration may have consequences on growth and tumorigenesis. ABSTRACT: Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or promoter functions according to the tissue context and we discuss the role of NSD1 in melanoma. Finally, we examine the ongoing efforts to target NSD1 signaling in cancers.