ezH

EzH refers to a family of proteins that are the catalytic components of the Polycomb repressive complex 2 (PRC2). They are histone methyltransferases that tri-methylate histone H3 on lysine 27 (H3K27me3), a chromatin mark associated with transcriptional repression. In mammals, the EzH family includes EZH1 and EZH2, both containing a SET domain and functioning with core subunits EED and SUZ12 to deposit H3K27me3 at target genes.

EZH2 is the predominant catalytic subunit in proliferating and embryonic cells, while EZH1 maintains H3K27me3 in differentiated cells. PRC2 silences a broad set of developmental regulators and lineage specification genes, contributing to cellular identity and stem cell function. Dysregulation of EZH2—through overexpression or activating mutations—has been linked to various cancers and developmental disorders.

Therapeutic relevance: Inhibitors targeting EZH2 have advanced to clinical use, with the drug tazemetostat approved for epithelioid sarcoma and certain lymphomas. Other EZH2 inhibitors are in trials, and research continues on resistance mechanisms, combination therapies, and context-dependent effects.

History and nomenclature: The name Enhancer of Zeste originates from Drosophila genetics; EZH1 and EZH2 are mammalian homologs identified in the late 1990s to early 2000s as part of Polycomb group–mediated chromatin silencing.