EZH2 and hepatocellular carcinoma: For example, histone modifications, collaboratively caused by enhancers of zeste homolog 2 (EZH2)-mediated H3 lysine 27 trimethylation (H3K27me3) and the deacetylation of lysine residues on histone H3 and H4, contribute to REX1 downregulation and the subsequently enhanced self-renewal properties, as evidenced by the decreased frequency of TIC observed in REX1-overexpressing HCC xenografts [60].