EZH2 was initially identified as a homolog of the drosophila Enhancer of Zeste through exon trap screening of chromosome 21. Both EZH2 and the related protein EZH1 can form complexes with the noncanonical Polycomb repressive complex-2 (PRC2) and maintain repressive chromatin, but the PRC2-EZH1 complex mediates methylation of histone H3. Both EZH1 and EZH2 are thought to function in the maintenance of embryonic stem cell pluripotency and plasticity and recently have been shown to be essential for hair follicle homeostasis and wound repair. Overexpression of EZH2 has been reported as a marker for advanced and metastatic cancers.

Human.

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Enhancer of Zeste homolog 2 (Ezh2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone H3. It has been shown that Akt phosphorylates Ezh2 at serine 21 and suppresses its methyltransferase activity by impeding Ezh2 binding to histone H3, which results in a decrease of lysine 27 trimethylation and derepression of silenced genes (1). Ezh2 interacts specifically with Vav both in vitro and in vivo. ENX-1 represents the human homolog of the Drosophila Enhancer of zeste gene, a member of the Polycomb group of genes, which are transcriptional regulators of homeobox gene expression.(2). Ezh2 is an essential epigenetic regulator of embryonic development in mice, but its role in the adult organism is unknown. High expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in lymphopoiesis. Data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development (3).