SUZ12

SUZ12 (suppressor of zeste 12 homolog) is a nuclear protein that serves as a core component of the Polycomb Repressive Complex 2 (PRC2). PRC2 mediates trimethylation of histone H3 on lysine 27 (H3K27me3), a repressive chromatin mark associated with transcriptional silencing. SUZ12 functions together with EZH2 (or EZH1) and EED, and with RBBP4/7 in mammals, to catalyze and propagate H3K27me3 across chromatin. The activity of PRC2 depends on SUZ12, and loss of SUZ12 disrupts histone methyltransferase activity and reduces H3K27me3 levels.

SUZ12 contains a conserved VEFS domain near its C-terminus, which is essential for PRC2 activity and for proper targeting of the complex to chromatin. The N-terminal region contributes to interactions with EZH2 and EED, and the full assembly stabilizes the catalytic core. SUZ12 helps recruit PRC2 to developmentally important loci and modulates substrate recognition and complex stability, thereby influencing gene expression programs during development and in stem cells.

Expression of SUZ12 is widespread in many cell types, and its function is important for embryonic development and maintenance of pluripotency. In experimental systems, SUZ12 deficiency leads to reduced H3K27me3 and derepression of differentiation-associated genes, with defects in cell fate decisions.

Alterations in SUZ12 or other PRC2 components have been observed in human diseases, including cancers and developmental disorders, reflecting the role of PRC2-mediated gene silencing in regulating growth and differentiation. SUZ12 is evolutionarily conserved, with homologs identified from invertebrates to vertebrates, reflecting its fundamental role in chromatin regulation.