Nucleotide variation in histone H2BL promotes cell proliferation by upregulating c-Myc

We found a histone H2B mutation, H2BL-T11C (leading to L3P amino acid variation) from tissue samples. Cells overexpressing H2BL-L3P showed stronger proliferation, colony formation and tumorigenic abilities. We further demonstrated that overexpressing H2BL-L3P made the cell cycle distribution changed via upregulation of c-Myc expression level. Furthermore, cell cycle studies based on EdU staining revealed the importance of c-Myc in promoting cell cycle progression through the G1/S checkpoint. As expected, treatment with 10058-F4, an inhibitor of the c-Myc-MAX interaction, alleviated the cell proliferation and cell cycle distribution phenotypes in the H2BL-L3P group and partially inhibited tumour growth. Overall, the amino acid mutation L3P, resulting from a SNP at a histone H2B locus, is associated with tumorigenesis and tumour progression. Additionally, the mechanisms and inhibitors involved in this study may provide a theoretical basis for targeted treatment of cancers with the same mutation. Overall design: Three independent replacations from each group of samples of SMMC-7721 cell lines (H2BG,H2BL and H2BL-L3P) with stable expression were collected and used for high-throughput RNA sequencing.