Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb repressive complex 2 (PRC2), has attracted broad research attention in the past few years because of its involvement in the development and maintenance of many types of cancer and the use of specific EZH2 inhibitors in clinical trials. Several observations show that PRC2 can have both oncogenic and tumour-suppressive functions. We propose that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes.
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The authors thank members of the Helin laboratory for discussions. The work in the Helin laboratory is supported by The European Research Council (294666_DNAMET), the 7th framework programme of the European Union (4DCellFate and INGENIUM), the Danish Cancer Society, the Danish National Research Foundation (DNRF 82), the Danish Council for Strategic Research, the Danish Medical Research Council, the Novo Nordisk Foundation, The Lundbeck Foundation and through a centre grant from the Novo Nordisk Foundation (the Novo Nordisk Foundation Section for Stem Cell Biology in Human Disease).
The authors declare no competing financial interests.
Supplementary information S1 (table) | Tumor sample analyses reveal that both gain and loss-offunction alterations of PRC2 occur in cancer (PDF 144 kb)
Supplementary information S2 (table) | Functional analyses reveal that PRC2 can play both oncogenic and tumour-suppressor roles (PDF 218 kb)
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Comet, I., Riising, E., Leblanc, B. et al. Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. Nat Rev Cancer 16, 803–810 (2016). https://doi.org/10.1038/nrc.2016.83
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