EZH2 and neoplasm: In proliferating cells, many tumor-suppressor genes or senescence effectors are silenced by PRC2 (e.g., p16 and the CDKN2A gene at the INK4A locus), and in senescent cells, the transcriptional downregulation of EZH2 leads to a loss of H3K27me3 and the activation of PRC2-mediated genes (Bracken et al., 2007; Maertens et al., 2009).