Enhancer of zeste homolog 2 (EZH2), with EED and SUZ12, forms the polycomb repressive complex 2 (PRC2), which catalyzes histone H3 lysine 27 (H3K27) methylation. Canonically, EZH2 is well known to repress transcription by mediating H3K27 tri-methylation (H3K27me3) at target gene promoters. In this study, we report that EZH2 non-canonically regulates transcription of SET/TAF-Iβ, known as a subunit of inhibitor of acetyltransferases (INHAT) complex and as a proto-oncogene. Importantly, transcriptional regulation of SET/TAF-Iβ by EZH2 was independent of PRC2 and its methyltransferase activity. Moreover, EZH2 and SET/TAF-Iβ levels were positively correlated, and both genes were highly expressed in various cancers including colon cancer as indicated by the analysis of TCGA database. Taken together, our study suggests the non-canonical role of EZH2 as a transcriptional activator of SET/TAF-Iβ independent of methyltransferase function in colon cancer.
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