Although Polycomb target genes silenced by EZH2 seem more prone to be permanently silenced by DNA methylation, possibly as a consequence of direct recruitment of DNA methyltransferases DNMT1 and 3 to the PcG, recent studies in prostate cancer suggest that EZH2-mediated histone methylation and DNA methylation may indeed occur side by side in gene silencing (94,95). The gene discussed is EZH2; the disease is Familial prostate cancer.