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dc.contributor.authorBRACKEN, ADRIANen
dc.date.accessioned2012-06-28T12:13:29Z
dc.date.available2012-06-28T12:13:29Z
dc.date.issued2006en
dc.date.submitted2006en
dc.identifier.citationBracken AP, Dietrich N, Pasini D, Hansen KH and Helin K, Genome-wide Mapping of Polycomb Target Genes Unravels Their Roles in Cell Fate Transitions., Genes and Development, 20, 9, 2006, 1123 - 1136en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/64081
dc.descriptionPUBLISHEDen
dc.description.abstractThe Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer. Here, we identify their target genes using genome-wide location analysis in human embryonic fibroblasts. We find that Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy >1000 silenced genes with a strong functional bias for embryonic development and cell fate decisions. We functionally identify 40 genes derepressed in human embryonic fibroblasts depleted of the PRC2 components (EZH2, EED, SUZ12) and the PRC1 component, BMI-1. Interestingly, several markers of osteogenesis, adipogenesis, and chrondrogenesis are among these genes, consistent with the mesenchymal origin of fibroblasts. Using a neuronal model of differentiation, we delineate two different mechanisms for regulating PcG target genes. For genes activated during differentiation, PcGs are displaced. However, for genes repressed during differentiation, we paradoxically find that they are already bound by the PcGs in nondifferentiated cells despite being actively transcribed. Our results are consistent with the hypothesis that PcGs are part of a preprogrammed memory system established during embryogenesis marking certain key genes for repressive signals during subsequent developmental and differentiation processesen
dc.description.sponsorshipWe thank Simone Minardi at The Affymetrix Microarray Unit of The IFOM-IEO campus (Milan, Italy) for help with the expression array experiments, Matteo Cesaroni and Rehanah Boup for their help with data analysis, and Henrik Winther at DAKO (Denmark) for the production of anti-sera to CBX8. We thank Michael Lees and Claus S. S?rensen for critical reading of the manuscript and Anders H. Lund, Bruno Amati, Ernesto Guccione, Marco Ciro, and members of the Helin laboratory for discussions. This work was supported by grants from the Association for International Cancer Research, the Danish Cancer Society, the Novo Nordisk Foundation, the Danish Medical Research Council, the Danish Natural Science Research Council, and the European Commission?s 6th Framework Programme.en
dc.format.extent1123en
dc.format.extent1136en
dc.language.isoenen
dc.relation.ispartofseriesGenes and Developmenten
dc.relation.ispartofseries20en
dc.relation.ispartofseries9en
dc.rightsYen
dc.subjectdifferentiationen
dc.subjectPolycomben
dc.subjectchromatinen
dc.subjectepigeneticsen
dc.subjectstem cellsen
dc.titleGenome-wide Mapping of Polycomb Target Genes Unravels Their Roles in Cell Fate Transitions.en
dc.typeJournal Articleen
dc.contributor.sponsorEuropean Commissionen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/brackeaen
dc.identifier.rssinternalid50040en
dc.identifier.doihttp://dx.doi.org/10.1101/gad.381706en
dc.subject.TCDThemeCanceren
dc.subject.TCDThemeGenes & Societyen
dc.identifier.orcid_id0000-0002-1547-9443en


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