Enhancer of zeste homolog 1 protein (EZH1)

Enhancer of zeste homolog 1 protein (EZH1) is an enzyme encoded by the EZH1 gene. It acts as a **catalytic subunit of the Polycomb repressive complex 2 (PRC2)**, responsible for methylating lysine 27 of histone H3 (H3K27), which results in transcriptional repression of target genes[3][4][8]. EZH1 works in concert with a paralog, EZH2; while both share H3K27 methyltransferase activity, EZH1 generally has weaker activity and is less abundant in embryonic stem cells compared to EZH2[3][8]. EZH1 is essential for maintaining **stem cell pluripotency, regulating gene expression through chromatin modification, and contributing to hair follicle homeostasis and wound healing in some models**[4]. EZH1 has emerging evidence of pathogenic involvement in cancer—for example, its reduced expression predicts poor prognosis in triple-negative breast cancer[5], and dual inhibition of EZH1 and EZH2 is being explored for certain leukemias[2]. Recent rare variants have been linked to neurodevelopmental phenotypes[1]. Several small-molecule dual EZH1/EZH2 inhibitors are in development, and the mechanism centers on blocking the methyltransferase activity to restore expression of silenced tumor suppressor genes[2][3]. Safety concerns arise from possible effects on normal stem cells and tissue regeneration due to its role in epigenetic regulation[2].

Other names

Enhancer of zeste 1 polycomb repressive complex 2 subunitHistone-lysine N-methyltransferase EZH1Polycomb protein EZH1EZH1_HUMANQ92800

Inhibition of enzymatic methyltransferase activity, leading to reduced H3K27 methylation and derepression of silenced genes[2]. Disruption of PRC2-mediated epigenetic gene silencing[2].