These data demonstrate that while SMYD3 functions as a transcriptional activator for certain gene sets (group 2, gene clusters 1 and 2), which is concordant with previously reported work3,4, it also functions as a repressor for other gene sets (group 1, gene clusters 1 and 2) in HPV-negative HNSCC cells. The gene discussed is SMYD3; the disease is head and neck squamous cell carcinoma.