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Gene Review

Pc  -  Polycomb

Drosophila melanogaster

Synonyms: CG32443, CG7618, DmPc, Dmel\CG32443, PC, ...
 
 
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Disease relevance of Pc

 

High impact information on Pc

 

Biological context of Pc

  • We find that the Pc protein quantitatively covers large regulatory regions of repressed BX-C genes [7].
  • Finally, loss of function of the Pc gene and overexpression of Pc and ph trigger up-regulation and down-regulation, respectively, of CycA expression in embryos [8].
  • We have analyzed the domains required for the association of Psc with ph and Pc by using the yeast two-hybrid system and an in vitro protein-binding assay [9].
  • There are multiple BX-C elements that mediate Pc group control, which we call Pc group response elements (PREs), and they can work when removed from the normal BX-C context [10].
  • This allele appears to be a null mutation, and we have used it to determine the Psc zygotic null phenotype and to look at the interactions of a null allele of Psc with five other Pc group mutations [11].
 

Anatomical context of Pc

 

Associations of Pc with chemical compounds

  • We have elaborated a method, based on the in vivo formaldehyde cross-linking technique, that allows a substantial enrichment for Pc-interacting sites by immunoprecipitation of the cross-linked chromatin with anti-Pc antibodies [7].
  • Stable transcriptional repression did not correlate with maintenance of YY1 or Polycomb DNA binding, but did correlate with persistence of histone H3 methylation on lysine 27 [17].
  • Additionally, using a Pc-beta gal fusion protein with deleted internal histidine repeats, we found that this mutant protein cannot bind to four particular target loci, but otherwise does not change the remaining overall binding pattern [18].
  • Here, we show that an immunoaffinity-purified Pc protein complex contains a DNA binding activity specific to the (GA)n motif in a PRE from the bithoraxoid region [19].
  • Methylammonium recognition involves two aromatic residues, not the three-residue aromatic cage used by chromodomains of HP1 and Polycomb proteins [20].
 

Physical interactions of Pc

  • Probes of chromatin accessibility in the Drosophila bithorax complex respond differently to Polycomb-mediated repression [21].
  • A Drosophila ESC-E(Z) protein complex is distinct from other polycomb group complexes and contains covalently modified ESC [22].
  • Importantly, we found that the PC-binding domain of PHO can mediate transcriptional repression in transfected Drosophila Schneider cells [23].
  • We show that ph and Psc coprecipitate with Pc from nuclear extracts [9].
  • Trl-GAGA directly interacts with lola like and both are part of the repressive complex of Polycomb group of genes [24].
 

Regulatory relationships of Pc

  • Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin [7].
  • We used Drosophila embryo and larval/imaginal disc transcriptional repression systems to determine whether YY1 repressed transcription in a manner consistent with PcG function in vivo [25].
  • In this article, we show that hh is maintained in a repressed state by the Polycomb group (PcG) chromatin proteins [26].
  • Asx alleles enhance both PcG and trxG homeotic transformations, showing that Asx is required for both the activation and the repression of homeotic loci [27].
  • These results demonstrate that CycA is directly regulated by PcG proteins, linking them to cell cycle control in vivo [8].
 

Other interactions of Pc

  • Here we have mapped the distribution of the Pc protein in the homeotic bithorax complex (BX-C) of Drosophila tissue culture cells [7].
  • Using LexA fusions, we show that PC and ESC can establish silencing of a reporter gene but that each requires the presence of the other [28].
  • We propose that PHO acts to anchor PcG protein complexes to DNA [29].
  • At the same stage, TRX but not PC is strongly associated with core promoters [30].
  • To identify additional genes involved in the determination of segmental identity, we have isolated dominant modifers (both suppressors and enhancers) of polycomb and/or antennapedia mutations [31].
 

Analytical, diagnostic and therapeutic context of Pc

References

  1. The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6). Boccuni, P., MacGrogan, D., Scandura, J.M., Nimer, S.D. J. Biol. Chem. (2003) [Pubmed]
  2. Transvection and silencing of the Scr homeotic gene of Drosophila melanogaster. Southworth, J.W., Kennison, J.A. Genetics (2002) [Pubmed]
  3. The Drosophila trithorax proteins contain a novel variant of the nuclear receptor type DNA binding domain and an ancient conserved motif found in other chromosomal proteins. Stassen, M.J., Bailey, D., Nelson, S., Chinwalla, V., Harte, P.J. Mech. Dev. (1995) [Pubmed]
  4. Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Tolhuis, B., de Wit, E., Muijrers, I., Teunissen, H., Talhout, W., van Steensel, B., van Lohuizen, M. Nat. Genet. (2006) [Pubmed]
  5. Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Schwartz, Y.B., Kahn, T.G., Nix, D.A., Li, X.Y., Bourgon, R., Biggin, M., Pirrotta, V. Nat. Genet. (2006) [Pubmed]
  6. RNAi components are required for nuclear clustering of Polycomb group response elements. Grimaud, C., Bantignies, F., Pal-Bhadra, M., Ghana, P., Bhadra, U., Cavalli, G. Cell (2006) [Pubmed]
  7. Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Orlando, V., Paro, R. Cell (1993) [Pubmed]
  8. Polycomb group-dependent Cyclin A repression in Drosophila. Martinez, A.M., Colomb, S., Déjardin, J., Bantignies, F., Cavalli, G. Genes Dev. (2006) [Pubmed]
  9. The Drosophila polycomb group protein Psc contacts ph and Pc through specific conserved domains. Kyba, M., Brock, H.W. Mol. Cell. Biol. (1998) [Pubmed]
  10. Elements of the Drosophila bithorax complex that mediate repression by Polycomb group products. Simon, J., Chiang, A., Bender, W., Shimell, M.J., O'Connor, M. Dev. Biol. (1993) [Pubmed]
  11. Phenotypic consequences and genetic interactions of a null mutation in the Drosophila Posterior Sex Combs gene. Adler, P.N., Martin, E.C., Charlton, J., Jones, K. Dev. Genet. (1991) [Pubmed]
  12. Stage-specific expression of polycomb group genes in human bone marrow cells. Lessard, J., Baban, S., Sauvageau, G. Blood (1998) [Pubmed]
  13. Mutations in some Polycomb group genes of Drosophila interfere with regulation of segmentation genes. McKeon, J., Slade, E., Sinclair, D.A., Cheng, N., Couling, M., Brock, H.W. Mol. Gen. Genet. (1994) [Pubmed]
  14. Effects of Polycomb group mutations on the expression of Ultrabithorax in the Drosophila visceral mesoderm. Choi, S.H., Oh, C.T., Kim, S.H., Kim, Y.T., Jeon, S.H. Mol. Cells (2000) [Pubmed]
  15. Direct interaction of the Polycomb protein with Antennapedia regulatory sequences in polytene chromosomes of Drosophila melanogaster. Zink, B., Engström, Y., Gehring, W.J., Paro, R. EMBO J. (1991) [Pubmed]
  16. Functional reconstruction of trans regulation of the Ultrabithorax promoter by the products of two antagonistic genes, trithorax and Polycomb. Chang, Y.L., King, B.O., O'Connor, M., Mazo, A., Huang, D.H. Mol. Cell. Biol. (1995) [Pubmed]
  17. Transient requirements of YY1 expression for PcG transcriptional repression and phenotypic rescue. Srinivasan, L., Pan, X., Atchison, M.L. J. Cell. Biochem. (2005) [Pubmed]
  18. Mapping functional domains of the polycomb protein of Drosophila melanogaster. Franke, A., Messmer, S., Paro, R. Chromosome Res. (1995) [Pubmed]
  19. pipsqueak encodes a factor essential for sequence-specific targeting of a polycomb group protein complex. Huang, D.H., Chang, Y.L., Yang, C.C., Pan, I.C., King, B. Mol. Cell. Biol. (2002) [Pubmed]
  20. Double chromodomains cooperate to recognize the methylated histone H3 tail. Flanagan, J.F., Mi, L.Z., Chruszcz, M., Cymborowski, M., Clines, K.L., Kim, Y., Minor, W., Rastinejad, F., Khorasanizadeh, S. Nature (2005) [Pubmed]
  21. Probes of chromatin accessibility in the Drosophila bithorax complex respond differently to Polycomb-mediated repression. McCall, K., Bender, W. EMBO J. (1996) [Pubmed]
  22. A Drosophila ESC-E(Z) protein complex is distinct from other polycomb group complexes and contains covalently modified ESC. Ng, J., Hart, C.M., Morgan, K., Simon, J.A. Mol. Cell. Biol. (2000) [Pubmed]
  23. Pleiohomeotic can link polycomb to DNA and mediate transcriptional repression. Mohd-Sarip, A., Venturini, F., Chalkley, G.E., Verrijzer, C.P. Mol. Cell. Biol. (2002) [Pubmed]
  24. Trl-GAGA directly interacts with lola like and both are part of the repressive complex of Polycomb group of genes. Mishra, K., Chopra, V.S., Srinivasan, A., Mishra, R.K. Mech. Dev. (2003) [Pubmed]
  25. Transcription factor YY1 functions as a PcG protein in vivo. Atchison, L., Ghias, A., Wilkinson, F., Bonini, N., Atchison, M.L. EMBO J. (2003) [Pubmed]
  26. Tissue specificity of hedgehog repression by the Polycomb group during Drosophila melanogaster development. Chanas, G., Maschat, F. Mech. Dev. (2005) [Pubmed]
  27. The Additional sex combs gene of Drosophila is required for activation and repression of homeotic loci, and interacts specifically with Polycomb and super sex combs. Milne, T.A., Sinclair, D.A., Brock, H.W. Mol. Gen. Genet. (1999) [Pubmed]
  28. Establishment of Polycomb silencing requires a transient interaction between PC and ESC. Poux, S., Melfi, R., Pirrotta, V. Genes Dev. (2001) [Pubmed]
  29. The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Brown, J.L., Mucci, D., Whiteley, M., Dirksen, M.L., Kassis, J.A. Mol. Cell (1998) [Pubmed]
  30. Binding of trithorax and Polycomb proteins to the bithorax complex: dynamic changes during early Drosophila embryogenesis. Orlando, V., Jane, E.P., Chinwalla, V., Harte, P.J., Paro, R. EMBO J. (1998) [Pubmed]
  31. Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Kennison, J.A., Tamkun, J.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  32. Transcriptional repression by Drosophila and mammalian Polycomb group proteins in transfected mammalian cells. Bunker, C.A., Kingston, R.E. Mol. Cell. Biol. (1994) [Pubmed]
  33. Trithorax- and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences. Tillib, S., Petruk, S., Sedkov, Y., Kuzin, A., Fujioka, M., Goto, T., Mazo, A. Mol. Cell. Biol. (1999) [Pubmed]
 
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