EZH2

EZH2 Full Name

enhancer of zeste homolog 2 (Drosophila)

EZH2 Introduction

EZH2, or enhancer of zeste homolog 2, is a histone methyltransferase that serves as the catalytic component of the Polycomb Repressive Complex 2 (PRC2), a major epigenetic regulator responsible for transcriptional silencing. By catalyzing the trimethylation of histone H3 at lysine 27 (H3K27me3), EZH2 establishes repressive chromatin states that control gene expression programs essential for development, differentiation, and stem cell maintenance. Originally identified as the mammalian homolog of a Drosophila Polycomb-group protein, EZH2 has since emerged as a key molecular switch that governs epigenetic memory and cellular identity. Its expression is normally high in proliferative tissues but becomes dysregulated under oncogenic or inflammatory conditions.

Figure 1. The molecular mechanisms of the role of enhancer of zeste homolog 2 (EZH2) in a polycomb repressive complex 2 (PRC2)-independent manner.(Sources: Jinhua Huang, et al.; 2021)

Functionally, EZH2 regulates a wide spectrum of cellular processes, including cell-cycle progression, lineage commitment, DNA repair, and chromatin organization. By repressing genes involved in differentiation, EZH2 helps preserve stemness and supports rapid proliferative capacity. It also interacts with transcription factors, long non-coding RNAs, and signaling pathways such as PI3K/AKT and JAK/STAT, expanding its influence beyond chromatin remodeling to broader transcriptional networks. Experimental studies show that loss of EZH2 disrupts chromatin structure and promotes premature differentiation, whereas its overactivation enhances proliferation, inhibits apoptotic pathways, and promotes tumorigenic transformation. Mutations in EZH2 that increase its methyltransferase activity further intensify transcriptional repression, contributing to aggressive cellular phenotypes.

Clinically, EZH2 is strongly implicated in cancer and serves as both a diagnostic and therapeutic target. Gain-of-function mutations in EZH2 are characteristic of certain B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, where they drive malignant progression through excessive H3K27me3 accumulation. Overexpression of EZH2 is also linked to poor prognosis in solid tumors such as prostate, breast, lung, and ovarian cancers, supporting metastasis, immune evasion, and resistance to therapy. Beyond oncology, dysregulated EZH2 activity contributes to developmental disorders, fibrosis, and inflammatory diseases through aberrant gene repression and altered tissue remodeling. These disease associations highlight EZH2 as a central epigenetic regulator whose modulation holds significant promise for precision medicine, particularly with the ongoing development of selective EZH2 inhibitors for targeted cancer therapy.

Alternate Names for EZH2

EZH2; enhancer of zeste homolog 2 (Drosophila); WVS; ENX1; EZH1; KMT6; WVS2; ENX-1; EZH2b; KMT6A; histone-lysine N-methyltransferase EZH2; lysine N-methyltransferase 6;

• Immunohistochemistry Antibodies for Pathology

• 1. Jinhua Huang, et al.; The non-canonical role of EZH2 in cancer. Cancer Science. C BY-NC-ND 4.0. 2021112(6)