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. Methylation of Lys27 facilitates the recruitment of the second complex, PRC1, which ubiquitinylates histone H2A on Lys119. Embryonic ectoderm development protein is a component of the PRC2 complex, which together with Ezh2 and SUZ12 is absolutely required for histone methyl-transferase activity. EED, SUZ12 and EZH2 are overexpressed in various types of cancer, including tumors of the colon, breast, prostate and ovary.
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