The polycomb group proteins contribute to the maintenance of cell identity, stem cell self-renewal, cell cycle regulation, and oncogenesis by maintaining the silenced state of genes that promote cell lineage specification, cell death, and cell-cycle arrest. PcG proteins exist in two complexes that cooperate to maintain long-term gene silencing through epigenetic chromatin modifications. The first complex, EED-EZH2, is recruited to genes by DNA-binding transcription factors and methylates histone H3 on Lys27. This histone methyl-transferase activity requires the Ezh2, Eed, and Suz12 subunits of the complex. Histone H3 methylation at Lys27 facilitates the recruitment of the second complex, PRC1, which ubiquitinylates histone H2A on Lys119. Chromobox protein homolog 2 is a core component of the PRC1 complex, which binds to the H3K27me3 mark and recruits PRC1 for transcriptional repression. CBX2 is frequently overexpressed in various cancers, including breast, ovarian, and AR-independent prostate cancer, where it is associated with poor prognosis. Furthermore, elevated CBX2 expression levels correlate with larger tumor size, increased lymph node metastasis, and positive human epidermal growth factor receptor 2 status in breast cancer. Mutations in CBX2 have also been attributed to 46,XY disorders of sex development, at least partially due to misregulation of the NR5A1/SF1 gene.
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