EZH2

EZH2 is the catalytic methyltransferase subunit of the Polycomb Repressive Complex 2 (PRC2) and mediates transcriptional repression through trimethylation of histone H3 lysine 27 (H3K27me3), thereby regulating cell proliferation, differentiation, and developmental gene expression programs^[1][2][3]. Mechanistically, PRC2-dependent H3K27 methylation establishes repressive chromatin states and cooperates with other epigenetic silencing pathways to maintain stable suppression of target genes^[4][5]. Through this epigenetic mechanism, EZH2 controls critical biological processes including cell-cycle regulation, lineage commitment, and transcriptional programs linked to tissue homeostasis and disease development^[2][1]. In disease contexts, aberrant EZH2 expression or activity is frequently associated with cancer progression, where enhanced H3K27me3-mediated repression contributes to tumor cell proliferation, survival, invasion, metastasis, and drug resistance^[2][3][6]. Experimental studies further demonstrate that EZH2 silencing can inhibit tumor growth and metastatic dissemination while restoring expression of tumor-suppressive genes, supporting its functional role in oncogenic epigenetic regulation^[6]. Compared with the related isoform EZH1, EZH2 is generally regarded as the dominant catalytic component driving PRC2 methyltransferase activity in proliferating cells and is therefore the principal focus of therapeutic targeting strategies directed at PRC2-dependent chromatin regulation^[1][7]. For experimental applications, selective EZH2 inhibitors have become important tools for investigating PRC2 biology and epigenetic gene repression, and the clinical development of agents such as tazemetostat has validated EZH2 as a tractable target for mechanistic and translational research in cancer models^[7][8][9].