The authors focused their functional analysis on insulin like growth factor binding protein 4 (IGFBP4) and showed that SMYD3 and the NuRD complex co-occupied the promoter of IGFBP4, and that knockdown of SMYD3 led to a decrease in H4K20me3 and a concomitant increase in H4 acetylation of the IGFBP4 promoter, resulting in transcriptional upregulation of this gene in HCC cells. Here, IGFBP4 is linked to hepatocellular carcinoma.