Enhancer of zeste homolog 2 polycomb repressive complex 2 subunit (EZH2)

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the Polycomb repressive complex 2 (PRC2), a key chromatin-modifying complex that mediates tri-methylation of lysine 27 on histone H3 (H3K27me3), leading to transcriptional silencing of target genes[1][3][5][10]. EZH2 regulates gene expression patterns that control development, cell fate, and proliferation, and is essential for maintaining epigenetic memory during cell division[1][3][5]. Dysregulation, mutation, or overexpression of EZH2 is implicated in a wide range of cancers (such as lymphomas, prostate cancer, and breast cancer) and other diseases involving aberrant cell proliferation, differentiation, or immune responses[2][3][4][6][8][10]. EZH2 is a clinically validated drug target, and inhibitors of its methyltransferase activity are approved for use (e.g., tazemetostat) or in clinical trials for epigenetic cancer therapies[10]. EZH2 also plays roles in immunity, stem cell biology, and kidney diseases, with complex, sometimes cell-type-specific outcomes[2][6][8]. Major challenges of therapy include balancing anti-tumor activity with potential risks of impaired normal cell function and immune dysregulation[8][10].

Other names

Enhancer of zeste homolog 2Enhancer of zeste 2EZH2KMT6Histone-lysine N-methyltransferase EZH2

Inhibition of histone methyltransferase activity, mainly at H3K27 Blockade of PRC2-mediated chromatin compaction and gene silencing Reactivation of tumor suppressor genes Modulation of differentiation and cell identity pathways