Importantly, Zinc finger E-box binding homeobox 1 (ZEB1), a major driver of EMT which was previously reported as a direct gene target of mouse Smyd3 in HCC and colon cancer mouse models3, was co-occupied by SMYD3 and H3K4me3 and was significantly downregulated by nearly 60% in the SMYD3 KO state (Supplementary Table 5, Supplementary Fig. 7). This evidence concerns the gene ZEB1 and hepatocellular carcinoma.