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. Polycomb group proteins regulate cell proliferation and senescence through repression of the p16Ink4a and p19Arf genes, and are essential in maintaining adult hematopoietic, neural stem cells, and embryonic stem cells. PcG proteins are found in two complexes that cooperate to maintain long-term gene silencing through epigenetic chromatin modifications. DNA-binding transcription factors recruit the EED-EZH2 complex to genes, which methylates histone H3 on Lys27. Methylation of Lys27 facilitates the recruitment of the PRC1 complex, which ubiquitinylates histone H2A on Lys119. PRC1 is composed of BMI1 and RING1A, which enhance the E3 ubiquitin ligase activity of the RING1B catalytic subunit. Polyhomeotic-like 1 is one of several additional PRC1 complex proteins that are required to maintain the silenced state of PRC1 target genes and mediate proper anterior-posterior specification during development. Mutations in the corresponding PHC1 gene correlate with an autosomal recessive form of primary microcephaly characterized by low-to-normal cognitive function and impaired DNA repair.
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