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Genome-wide analysis of Polycomb targets in Drosophila melanogaster

Nature Genetics volume 38, pages 700–705 (2006)Cite this article

Abstract

Polycomb group (PcG) complexes are multiprotein assemblages that bind to chromatin and establish chromatin states leading to epigenetic silencing1,2. PcG proteins regulate homeotic genes in flies and vertebrates, but little is known about other PcG targets and the role of the PcG in development, differentiation and disease. Here, we determined the distribution of the PcG proteins PC, E(Z) and PSC and of trimethylation of histone H3 Lys27 (me3K27) in the D. melanogaster genome. At more than 200 PcG target genes, binding sites for the three PcG proteins colocalize to presumptive Polycomb response elements (PREs). In contrast, H3 me3K27 forms broad domains including the entire transcription unit and regulatory regions. PcG targets are highly enriched in genes encoding transcription factors, but they also include genes coding for receptors, signaling proteins, morphogens and regulators representing all major developmental pathways.

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Figure 1: Distribution of PcG proteins and H3 me3K27 mark on chromosome 3R.
Figure 2: PcG and me3K27 profile at the Bithorax complex.
Figure 3: PC and me3K27 bind to much broader regions than PSC or E(Z).
Figure 4: Profiles of me3K27 and PcG proteins at representative PcG sites.
Figure 5: NK homeodomain cluster and dco-Sox10B0 site.
Figure 6: Genes encoding regulators of transcription are greatly enriched among PcG targets.

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References

  1. Pirrotta, V. PcG complexes and chromatin silencing. Curr. Opin. Genet. Dev. 7, 249–258 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Lund, A.H. & van Lohuizen, M. Polycomb complexes and silencing mechanisms. Curr. Opin. Cell Biol. 16, 239–246 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Rastelli, L., Chan, C.S. & Pirrotta, V. Related chromosome binding sites for zeste, suppressors of zeste and Polycomb group proteins in Drosophila and their dependence on Enhancer of zeste function. EMBO J. 12, 1513–1522 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chan, C.-S., Rastelli, L. & Pirrotta, V. A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression. EMBO J. 13, 2553–2564 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sengupta, A.K., Kuhrs, A. & Muller, J. General transcriptional silencing by a Polycomb response element in Drosophila. Development 131, 1959–1965 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Saurin, A.J., Shao, Z., Erdjument-Bromage, H., Tempst, P. & Kingston, R.E. A Drosophila Polycomb group complex includes Zeste and dTAFII proteins. Nature 412, 655–660 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Czermin, B. et al. Drosophila Enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111, 185–196 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. Cao, R. et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039–1043 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P. & Reinberg, D. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 22, 2893–2905 (2002).

    Article  Google Scholar 

  10. Müller, J. et al. Histone methyltransferase activity of a Drosophila Polycomb Group repressor complex. Cell 111, 197–208 (2002).

    Article  PubMed  Google Scholar 

  11. Fischle, W. et al. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev. 17, 1870–1881 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jones, R.S. & Gelbart, W.M. Genetic analysis of the Enhancer of zeste locus and its role in gene regulation in Drosophila melanogaster. Genetics 126, 185–199 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Phillips, M.D. & Shearn, A. Mutations in polycombeotic, a Drosophila Polycomb-group gene, cause a wide range of maternal and zygotic phenotypes. Genetics 125, 91–101 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Strutt, H. & Paro, R. The polycomb group protein complex of Drosophila melanogaster has different composition at different target genes. Mol. Cell. Biol. 17, 6773–6783 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bloyer, S., Cavalli, G., Brock, H.W. & Dura, J.-M. Identification and characterization of polyhomeotic PREs and TREs. Dev. Biol. 261, 426–442 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Reim, I., Lee, H.-H. & Frasch, M. The T-box-encoding Dorsocross genes function in amnioserosa development and the patterning of the dorsolateral germ band downstream of Dpp. Development 130, 3187–3204 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Jagla, K., Bellard, M. & Frasch, M. A cluster of Drosophila homeobox genes involved in mesoderm differentiation programs. Bioessays 23, 125–133 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Chiang, A., O'Connor, M.B., Paro, R., Simon, J. & Bender, W. Discrete Polycomb-binding sites in each parasegmental domain of the bithorax complex. Development 121, 1681–1689 (1995).

    CAS  PubMed  Google Scholar 

  19. Shimell, M.J., Peterson, A.J., Burr, J., Simon, J.A. & O'Connor, M. Functional analysis of repressor binding sites in the iab-2 regulatory region of the abdominal-A homeotic gene. Dev. Biol. 218, 38–52 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Busturia, A., Wightman, C.D. & Sakonju, S. A silencer is required for maintenance of transcriptional repression throughout Drosophila development. Development 124, 4343–4350 (1997).

    CAS  PubMed  Google Scholar 

  21. Mihaly, J., Hogga, I., Gausz, J., Gyurkovics, H. & Karch, F. In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element. Development 124, 1809–1820 (1997).

    CAS  PubMed  Google Scholar 

  22. Barges, S. et al. The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain. Development 127, 779–790 (2000).

    CAS  PubMed  Google Scholar 

  23. Orlando, V. & Paro, R. Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell 75, 1187–1198 (1993).

    Article  CAS  PubMed  Google Scholar 

  24. Gene Ontology Consortium. The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32, D258–D261 (2004).

  25. Ringrose, L., Rehmsmeier, M., Dura, J.M. & Paro, R. Genome-wide prediction of Polycomb/Trithorax response elements in Drosophila melanogaster. Dev. Cell 5, 759–771 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Brunk, B.P., Martin, E.C. & Adler, P.N. Drosophila genes Posterior Sex Combs and Suppressor two of zeste encode proteins with homology to the murine bmi-1 oncogene. Nature 353, 351–353 (1991).

    Article  CAS  PubMed  Google Scholar 

  27. Lee, T.I. et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125, 301–313 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bernstein, B.E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Négre, N. et al. Chromosomal distribution of PcG proteins during Drosophila development. PLoS Biol. 4, e170 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Schneider, I. Cell lines derived from the late embryonic stages of Drosophila melanogaster. J. Embryol. Exp. Morphol. 27, 353–356 (1972).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to T. Jenuwein for the anti-H3 me3K27 antibody; to D. McCabe for polytene chromosome preparations; to A. Brooks, Q. Wang and V. Patel of the Bionomics Research and Technology Center of the Rutgers Environmental and Occupational Health Sciences Institute for hybridization and scanning of the microarrays. Particular thanks to M. Eisen for leading the Berkeley Drosophila Transcription Network Project's development of ChIP/chip data analysis methods and for encouraging this work. Work conducted by the BDTNP is funded by a grant from the US National Institute of General Medical Sciences and the US National Human Genome Research Institute (GM704403) at Lawrence Berkeley National Laboratory under Department of Energy contract DE-AC02-05CH11231.

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Authors and Affiliations

  1. Department of Molecular Biology and Biochemistry, Rutgers University, 604 Allison Road, Piscataway, 08854, New Jersey, USA

    Yuri B Schwartz, Tatyana G Kahn & Vincenzo Pirrotta

  2. Genomics Division, Berkeley Drosophila Transcription Network Project, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    David A Nix, Xiao-Yong Li & Mark Biggin

  3. Department of Statistics, University of California, Berkeley, Berkeley, 94720, California, USA

    Richard Bourgon

  4. Affymetrix, 6550 Vallejo Street, Emeryville, 94608, California, USA

    David A Nix

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Correspondence to Vincenzo Pirrotta.

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D.A.N. is employed by Affymetrix.

Supplementary information

Supplementary Fig. 1

Distribution of PcG proteins and H3 me3K27 mark along the X chromosome. (PDF 81 kb)

Supplementary Fig. 2

Distribution of PcG proteins and H3 me3K27 mark along chromosome 4. (PDF 84 kb)

Supplementary Fig. 3

Distribution of PcG proteins and H3 me3K27 mark along 2L chromosome. (PDF 83 kb)

Supplementary Fig. 4

Distribution of PcG proteins and H3 me3K27 mark along 2R chromosome. (PDF 81 kb)

Supplementary Fig. 5

Distribution of PcG proteins and H3 me3K27 mark along 3L chromosome. (PDF 82 kb)

Supplementary Fig. 6

Co-localization between the binding of PSC and other PcG proteins. (PDF 44 kb)

Supplementary Fig. 7

Co-localization between the binding of E(Z) and other PcG proteins. (PDF 42 kb)

Supplementary Fig. 8

Comparison of microarray data to the Ringrose et al. genome-wide prediction of PREs. (PDF 21 kb)

Supplementary Fig. 9

PcG proteins bind to ph and Psc-Su(z)2 polycomb group genes. (PDF 129 kb)

Supplementary Fig. 10

Valication of microarray hybridization results by real-time PCR. (PDF 207 kb)

Supplementary Table 1

List of PcG sites. (PDF 196 kb)

Supplementary Table 2

General features of PcG sites. (PDF 53 kb)

Supplementary Table 3

List of PCR primers. (PDF 69 kb)

Supplementary Methods (PDF 62 kb)

Supplementary Note (PDF 12 kb)

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Schwartz, Y., Kahn, T., Nix, D. et al. Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet 38, 700–705 (2006). https://doi.org/10.1038/ng1817

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