Polycomb or Pc-G bodies were first identified in the transformed human cell line U2-OS (Alkema et al., 1997) . Staining these cells with antibodies against the mammalian polycomb group protein Bmi1 revealed a punctate pattern reminiscent of the speckled distribution of PML bodies (Alkema et al., 1997) . Pc-G bodies have subsequently been identified in a number of transformed mouse and human cell lines (Voncken et al., 1999) . However, there is little evidence that Pc-G bodies exist outside of the tissue culture flask. The sub-cellular distribution of three Pc-G group proteins has been studied in Drosophila embryos (Buchenau et al., 1998). The punctate staining pattern seen previously in mammalian cells was not reproduced here and a more diffuse nuclear staining was observed. Furthermore, primary mammalian cells lack Pc-G bodies, unless passaged for prolonged periods in tissue culture (Voncken et al., 1999) .

Polycomb protein function

Although Pc-G bodies may well be a curiosity of the in vitro environment, the Pc-G proteins are of clear importance from flies to mammals (Gould 1997). The Pc-G genes of Drosophila, such as Posterior sex combs (Psc) and Supressor-two-of-zeste are required to maintain the correct patterns of Hox gene transcription. Loss of gene Pc-G function in flies leads to mis-expression of Hox genes, causing the homeotic transformation of embryo parts. The role of Pc-G proteins in transcriptional repression may occur via discrete DNA elements. Stable silencing probably involves large protein complexes, although these might not be packaged into compact heterochromatin. The effects of Pc-G proteins in flies are broadly antagonistic to those of the trithorax group (trxG) genes. One such gene encodes the DNA-dependent ATPase/helicase brahma, which is related to a component of the SWI/SNF complex in budding yeast.

Mammalian homologues of the Polycomb proteins

Mammalian homologs of the Pc-G genes have been identified, with conserved sequences and apparently conserved functions (Gould 1997). The homologs of Psc in mice, Bmi1 and Mel18, have several motifs in common with Psc, notably a RING finger, which is implicated in target site specificity. Disruption of the genes encoding Mel18 and Bmi1 in mice gives rise to phenotypes consistent with a role for the mammalian Pc-G proteins in regulating Hox expression. Several hox genes are mis-expressed in both mutants and the mice show vertebral tranformations which have been interpreted as homeotic phenotypes. A third mouse Pc-G protein, M33, which shares the chromodomain of Psc, can partially rescue Drosophila Pc-G loss of function, suggesting this may be the true homolog (Muller et al., 1995) . Loss of M33 in mice also results in homeotic-like transformations. Another mammalian Pc-G gene, eed, is homologous to the Drosophila Pc-G gene extra sex combs (Core et al., 1997) . Loss of eed function interferes with gastrulation in mice, but may have roles in Hox regulation later in embryogenesis (Faust et al., 1995) .

  • Polycomb and Trithorax Resources from Rein Aasland

  • Polycomb gene information from the Interactive Fly

  • Renato Paro's Home Page-Chromatin and Epigenetics

  • Muller Group Pages--Mechanisms of transcriptional regulation in development of Drosophila

  • Drosophila Genes in Development: Polycomb-group

    Alkema MJ, Bronk M, Verhoeven E, Otte A, van't Veer LJ, Berns A, van Lohuizen M. (1997) Identification of Bmi1-interacting proteins as constituents of a multimeric mammalian polycomb complex. Genes Dev. 11(2):226-240.

    Buchenau P, Hodgson J, Strutt H, Arndt-Jovin DJ. (1998) The distribution of polycomb-group proteins during cell division and development in Drosophila embryos: impact on models for silencing. J. Cell Biol. 141(2):469-481.

    Core N, Bel S, Gaunt SJ, Aurrand-Lions M, Pearce J, Fisher A, Djabali M. (1997) Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice. Development 124(3):721-729.

    Faust C, Schumacher A, Holdener B, Magnuson T. (1995) The eed mutation disrupts anterior mesoderm production in mice. Development 121(2):273-285.

    Gould, A. (1997) Functions of mammalian Polycomb group and trithorax group related genes. Curr. Opin .Genet. Dev. 7(4):488-494

    Muller J, Gaunt S, Lawrence PA. (1995) Function of the Polycomb protein is conserved in mice and flies. Development. 121(9):2847-2852

    Voncken JW, Schweizer D, Aagaard L, Sattler L, Jantsch MF, van Lohuizen M. (1999) Chromatin-association of the Polycomb group protein BMI1 is cell cycle-regulated and correlates with its phosphorylation status. J. Cell Sci. 112 ( 24):4627-4639