ID4 and prostate cancer: While Id4 is highly expressed in normal prostate epithelial cells, it decreases in prostate cancer cells in a stage-dependent manner and correlating with Id4 promoter hypermethylation trough enhancer of Zeste 2 (EZH2)-dependent trimethylation of histone 3 at lysine 27 [222], which results in no Id4 expression in high-grade cancers.