Although histone methylation mediated by methyltransferases usually induces gene downregulation, EZH2 has been reported to positively regulate gene expression in cancers through direct methylation of potential non-histone proteins (Xu et al., 2012) including signal transducer and activator of transcription 3 (STAT3; Kim et al., 2013). The gene discussed is H2BC12L; the disease is cancer.