PRC2

Polycomb repressive complex 2 (PRC2) is a conserved multi-subunit histone methyltransferase that establishes and maintains transcriptionally repressed chromatin. In mammals, its core catalytic subunit is EZH2, with EZH1 as a related paralog. The enzymatic activity of PRC2 centers on trimethylation of histone H3 at lysine 27 (H3K27me3). The core components include SUZ12, EED, and the histone-binding protein RBBP4/7. Additional subunits and accessory factors modulate activity, recruitment, and targeting, such as AEBP2, JARID2, the Polycomb-like (PCL) proteins PHF1/MTF2/PHF19, and PALI1/2 in some lineages.

Mechanism and recruitment: PRC2 catalyzes H3K27me3 on nucleosomes; EED recognizes existing H3K27me3 and stimulates allosterically the catalytic activity, enabling spreading of the repressive mark. Recruitment to chromatin is guided by pre-existing chromatin features, CpG-rich islands, non-coding RNAs including XIST in X-chromosome inactivation, and interacting transcription factors and accessory subunits. The modified chromatin can recruit additional PRC2 and maintain silencing across cell generations.

Function and significance: PRC2 plays a crucial role in development, stem cell maintenance, and lineage commitment by repressing gene expression programs inappropriate for a given cell type. It also participates in genomic imprinting and X-chromosome inactivation. Aberrant PRC2 activity is linked to disease, notably cancers such as lymphomas and solid tumors; EZH2 mutations can have gain- or loss-of-function effects depending on context, and dysregulation of SUZ12 and EED has been observed in tumors.

History: PRC2 is part of the Polycomb group of repressive complexes first characterized in Drosophila as regulators of homeotic genes. In vertebrates, the core subunits are conserved and include catalytic and scaffolding components that coordinate chromatin silencing through histone methylation. Research on PRC2 informs understanding of epigenetic regulation and developmental biology.