Epigenetic modifications, such as histone acetylation and methylation of H3K3me3.- Histone acetylation helps BET domain proteins (BRD4) to associate with PD-L1. Also, HDAC inhibitors augment histone acetylation and upregulate PD-L1 expression in tumors (28–30).- Trimethylation of histone H3 on lysine 4 increases PD-L1 expression in cancer cells. For example, Histone methyltransferase (HMTase) MLL1 associate with CD274 promoter and catalyzes H3K4me3, thereby upregulating its expression, which in turn boosts PD-L1 mRNA levels in tumors (31). The gene discussed is CD274; the disease is cancer.