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Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster

Nature Genetics volume 38, pages 694–699 (2006)Cite this article

A Corrigendum to this article was published on 01 July 2006

Abstract

Polycomb group (PcG) proteins maintain transcriptional repression of developmentally important genes1 and have been implicated in cell proliferation and stem cell self-renewal2. We used a genome-wide approach3 to map binding patterns of PcG proteins (Pc, esc and Sce) in Drosophila melanogaster Kc cells. We found that Pc associates with large genomic regions of up to ∼150 kb in size, hereafter referred to as 'Pc domains'. Sce and esc accompany Pc in most of these domains. PcG-bound chromatin is trimethylated at histone H3 Lys27 and is generally transcriptionally silent. Furthermore, PcG proteins preferentially bind to developmental genes. Many of these encode transcriptional regulators and key components of signal transduction pathways, including Wingless, Hedgehog, Notch and Delta. We also identify several new putative functions of PcG proteins, such as in steroid hormone biosynthesis. These results highlight the extensive involvement of PcG proteins in the coordination of development through the formation of large repressive chromatin domains.

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Figure 1: Pc binds large genomic regions or 'domains'.
Figure 2: PcG proteins bind largely to same genomic sites.
Figure 3: PcG-bound chromatin is trimethylated at Lys27 of histone H3.
Figure 4: PcG-bound chromatin is transcriptionally repressed.
Figure 5: Developmental expression of genes located within Pc domains.
Figure 6: Functional role of PcG proteins in Kc cells.

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Acknowledgements

We thank G. Cavalli and N. Nègre for sharing unpublished results and for providing Pc and ph antibodies; J. Müller for Su(z)12 antibody; F. Greil, H. Pickersgill, M. Heimerickx and the NKI Central Microarray Facility for technical assistance; M. Fornerod for sharing R scripts; H. Bussemaker for the Quontology script; the Genomics Facility of the Fred Hutchinson Cancer Research Center for preparing 12K cDNAs and A. Brinkman and H. Stunnenberg for help with ChIP. This work was supported by a Veni fellowship from the Netherlands Organisation for Scientific Research (NWO) to B.T., a fellowship from the Association of International Cancer Research to I.M., a Centre for Biomedical Genetics grant to M.v.L. and support from the European 'Epigenome' Network of Excellence and a European Young Investigator (EURYI) award to B.v.S.

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Author notes

  1. Inhua Muijrers and Elzo de Wit: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Molecular Genetics, and the Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands

    Bas Tolhuis, Inhua Muijrers, Elzo de Wit, Hans Teunissen, Wendy Talhout, Bas van Steensel & Maarten van Lohuizen

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  1. Bas Tolhuis
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Correspondence to Bas van Steensel or Maarten van Lohuizen.

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Supplementary information

Supplementary Fig. 1

PcG-Dam fusions incorporate into native PRCs. (PDF 60 kb)

Supplementary Fig. 2

Overview of all identified Pc domains. (PDF 1352 kb)

Supplementary Fig. 3

Pc, GAF and HP1 binding on the Adh-cactus region. (PDF 76 kb)

Supplementary Fig. 4

Correspondence between Pc binding analyzed on two microarray platforms. (PDF 89 kb)

Supplementary Fig. 5

Nuclear localization of endogenous Pc and HP1 proteins. (PDF 43 kb)

Supplementary Table 1

Binding ratios of reported PcG target genes. (PDF 30 kb)

Supplementary Table 2

Pc domains identified using genomic tiling arrays. (PDF 40 kb)

Supplementary Table 3

Quontology data PcG protein binding profiles. (XLS 255 kb)

Supplementary Table 4

Pc targets for each GO category enriched for Pc binding. (XLS 100 kb)

Supplementary Table 5

Pc targets in 'Ectoderm development' GO category. (PDF 49 kb)

Supplementary Table 6

Gene ontology on genes identified in Pc domains. (XLS 164 kb)

Supplementary Methods (PDF 14 kb)

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Tolhuis, B., Muijrers, I., de Wit, E. et al. Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nat Genet 38, 694–699 (2006). https://doi.org/10.1038/ng1792

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