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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We thank G. Cavalli and N. Nègre for sharing unpublished results and for providing Pc and ph antibodies; J. Müller for Su(z)12 antibody; F. Greil, H. Pickersgill, M. Heimerickx and the NKI Central Microarray Facility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.
The authors declare no competing financial interests.
PcG-Dam fusions incorporate into native PRCs. (PDF 60 kb)
Overview of all identified Pc domains. (PDF 1352 kb)
Pc, GAF and HP1 binding on the Adh-cactus region. (PDF 76 kb)
Correspondence between Pc binding analyzed on two microarray platforms. (PDF 89 kb)
Nuclear localization of endogenous Pc and HP1 proteins. (PDF 43 kb)
Binding ratios of reported PcG target genes. (PDF 30 kb)
Pc domains identified using genomic tiling arrays. (PDF 40 kb)
Quontology data PcG protein binding profiles. (XLS 255 kb)
Pc targets for each GO category enriched for Pc binding. (XLS 100 kb)
Pc targets in 'Ectoderm development' GO category. (PDF 49 kb)
Gene ontology on genes identified in Pc domains. (XLS 164 kb)
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