Enhancer of zeste homolog 1 (EZH1) (EZH1)

Enhancer of zeste homolog 1 (EZH1) is a protein-coding gene whose mRNA transcript is translated into a catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) (NCBI Gene ID: 2145). The EZH1 protein mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a critical epigenetic modification for gene silencing and chromatin compaction (UniProt Q92800). While its paralog EZH2 is the primary methyltransferase in proliferating cells, EZH1 is expressed in both dividing and non-dividing cells, providing a compensatory mechanism to maintain repressive marks when EZH2 is absent or inhibited (PMID: 26073138). In various cancers, including T-cell lymphomas and myeloid leukemias, EZH1 and EZH2 work redundantly to silence tumor suppressor genes, facilitating oncogenesis and treatment resistance (PMID: 31110145). Therapeutic strategies targeting this pathway often utilize dual EZH1/2 inhibitors like valemetostat, which block the enzymatic activity of the resulting proteins to restore normal gene expression patterns (PMID: 35760814). Although current clinical drugs primarily target the EZH1 protein, the EZH1 mRNA itself represents a potential target for nucleic acid-based therapies such as antisense oligonucleotides or RNA interference to modulate epigenetic states (PMID: 36108227).

Other names

ENX-2KMT6BEnhancer of zeste 1 polycomb repressive complex 2 subunit

Dual inhibition of EZH1 and EZH2 methyltransferase activity to prevent H3K27 trimethylation and restore tumor suppressor gene expression.