The role of the methyltransferase SETD6 in melanoma

Melanoma is the most lethal form of skin cancer however, despite the emergence of effective therapies, metastatic melanoma remains largely incurable. Histone and DNA methylation is a central epigenetic mechanism that regulates the pathobiology of melanoma. Signaling via lysine methylation by protein lysine methyltransferases (PKMTs) has been linked to diverse biological and disease processes. The mono-methyltransferase SETD6 (SET-domain-containing protein 6) is a member of the PKMT family and was previously shown to regulate essential cellular processes. We found that high levels of SETD6 were associated with a poor prognosis for melanoma patients. However, the role of SETD6 in melanoma was not explored yet.

Our results suggest that depletion of SETD6 in melanoma cells regulates gene expression, colony formation, adhesion, and apoptosis. Our genomic and biochemical data also suggest a functional cross-talk between SETD6 and the transcription factor BRD4 in regulating gene expression programs and cellular phenotypes related to melanoma.

Collectively, we discovered a link between SETD6 and melanoma development and progression. Our results support the importance of SETD6-mediated methylation in various cellular processes, thus establishing SETD6 and its substrates as possible regulators in different pathologies.