EZH2, the catalytic subunit of the PRC2 complex, has been shown to overexpress in different types of cancers. Oncogenic role of EZH2 originally was thought to exhibit through its Histone H3 K27 methyltransferase activity. In recent years, several studies, including ours, have highlighted new oncogenic roles of EZH2, either PRC2-independent, or as co-activator for other transcription factors in some context of cancers. Specifically in natural killer/ T cell lymphoma (NKTL), we have already uncovered that oncogenic role of EZH2 is independent of its methyltransferase function, and JAK3 switches EZH2 from a transcriptional repressor to an activator through direct phosphorylation thus conferring the lymphoma cells with growth advantage. What's more, we showed that JAK3, EZH2 and RNA POL II are in the same complex, whereas JAK3 does not stay together with PRC2 complex. In this study, in order to map all the interacting partners of PRC2 complex as well as EZH2-POL II complex, we used NKTL cell lines for SILAC Mass Spectrometry to identify interactome of EZH2, RNA POL II and PRC2 component SUZ12, respectively. Then we overlapped EZH2 and SUZ12 interactome for canonical factors assisting PRC2-mediated gene repression, as well as EZH2 and POL II interactome for non-canonical factors which might play a role in EZH2-regulated gene activation. Some of those non-canonical factors have been shown to display extraordinary high expression in EBV-positive lymphocytes among other cancerous and normal tissues (GTEx RNA-seq expression data), or in NKTL patient sample than normal NK cells (our own GEP data). Intriguingly, GO analysis of these three interactomes indicates that the major function of EZH2 in NKTL is realized mainly through the EZH2-POL II complex, rather than the PRC2 complex. These data reinforced the oncogenic role of EZH2-POL II complex in NKTL, and suggested new players in EZH2-mediated oncogenesis.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.