Alternative titles; symbols
HGNC Approved Gene Symbol: PHC2
Cytogenetic location: 1p35.1 Genomic coordinates (GRCh38): 1:33,323,626-33,431,095 (from NCBI)
In Drosophila melanogaster, the 'Polycomb' group (PcG) genes are part of a cellular memory system that is responsible for the stable inheritance of gene activity. PcG proteins form a large multimeric, chromatin-associated protein complex. Using a yeast 2-hybrid screen, Gunster et al. (1997) identified leukocyte cDNAs encoding a protein that interacted with BMI1 (164831), a vertebrate PcG protein. The protein was designated HPH2 because it had homology to the Drosophila PcG protein 'polyhomeotic' (Ph) as well as to mouse Rae28/Mph1 (see HPH1, 602978). All 3 proteins contain a zinc finger motif and 2 regions designated homology domains I and II. The results of 2-hybrid analysis indicated that homology domains I and II are involved in protein-protein interactions and may mediate heterodimerization of HPH1 and HPH2. HPH1 and HPH2 coimmunoprecipitate and cofractionate with each other and with BMI1. By immunofluorescence, Gunster et al. (1997) determined that all 3 proteins colocalize in large domains in interphase nuclei of human cells. The authors concluded that HPH1, HPH2, and BMI1 are part of a common, multimeric protein complex. Northern blot analysis revealed that HPH2 was expressed ubiquitously as a 2.5-kb transcript.
Wang et al. (2004) showed that an E3 ubiquitin ligase complex, which they designated Polycomb repressive complex-1-like (PRC1L), specifically monoubiquitinates histone-2A (H2A; see 142711) at lys119. They found that PRC1L is composed of several PcG proteins, including RING1 (602045), RNF2 (608985), BMI1, and HPH2. Reduction of RNF2 expression resulted in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Wang et al. (2004) proposed that H2A ubiquitination is linked to Polycomb silencing.
Gunster, M. J., Satijn, D. P. E., Hamer, K. M., den Blaauwen, J. L., de Bruijn, D., Alkema, M. J., van Lohuizen, M., van Driel, R., Otte, A. P. Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic. Molec. Cell. Biol. 17: 2326-2335, 1997. [PubMed: 9121482] [Full Text: https://doi.org/10.1128/MCB.17.4.2326]
Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R. S., Zhang, Y. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431: 873-878, 2004. [PubMed: 15386022] [Full Text: https://doi.org/10.1038/nature02985]