Nearly 99% of all H4K20me3 peaks were decreased or lost after A-196 or siSUV420H1 treatment, supporting that SUV420H1 is the primary regulator of H4K20me3 genomic deposition in HPV-negative HNSCC cells (Supplementary Fig. 8B, C). This evidence concerns the gene KMT5B and head and neck squamous cell carcinoma.