Yuan et al recently showed that SETD2 was able to methylate EZH2 at K735 to promote EZH2 degradation, which provides a mechanism for how H3K36m3 excludes H3K27me3 signals during prostate cancer development.[8b] However, in different contexts, whether and how H3K36me3 antagonizes H3K27me3 remains to be explored in depth. Here, SETD2 is linked to prostate carcinoma.