Polycomb

Polycomb refers to the Polycomb group (PcG) proteins, a family of conserved chromatin regulators that repress gene transcription. They were identified in Drosophila as key players in maintaining the silenced state of developmental genes across cell divisions, thereby helping to preserve cell identity during development.

PcG function is organized around two main complexes: Polycomb repressive complex 2 (PRC2) and Polycomb repressive complex 1 (PRC1). PRC2 contains core components such as EZH2 or EZH1 (the catalytic subunit), EED, and SUZ12, and it catalyzes the trimethylation of histone H3 on lysine 27 (H3K27me3). This histone mark helps recruit PRC1, which includes RING1A or RING1B and BMI1 among other subunits, and mediates monoubiquitination of histone H2A on lysine 119 (H2AK119ub). These marks promote chromatin compaction and transcriptional repression. In mammals, additional noncanonical PRC1 variants and accessory subunits modulate targeting and stability of repression.

PcG-mediated repression regulates a set of key developmental genes, including Hox loci, and contributes to maintaining pluripotency in stem cells while restricting differentiation. They also participate in X-chromosome inactivation and genomic imprinting in certain contexts. Abnormal PcG activity is linked to diseases such as cancer; EZH2, in particular, is frequently overexpressed or mutated in hematologic and solid tumors. Epigenetic therapies targeting EZH2 and other PcG components are under development, with EZH2 inhibitors approved for specific cancers.

PcG function is counterbalanced by the Trithorax group (TrxG) proteins, which promote gene activation. The PcG–TrxG balance helps regulate stable, heritable gene expression programs during development and differentiation.