dc.contributor.author | BRACKEN, ADRIAN | en |
dc.date.accessioned | 2012-06-28T12:13:29Z | |
dc.date.available | 2012-06-28T12:13:29Z | |
dc.date.issued | 2006 | en |
dc.date.submitted | 2006 | en |
dc.identifier.citation | Bracken 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 - 1136 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/64081 | |
dc.description | PUBLISHED | en |
dc.description.abstract | The 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 processes | en |
dc.description.sponsorship | We 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.extent | 1123 | en |
dc.format.extent | 1136 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Genes and Development | en |
dc.relation.ispartofseries | 20 | en |
dc.relation.ispartofseries | 9 | en |
dc.rights | Y | en |
dc.subject | differentiation | en |
dc.subject | Polycomb | en |
dc.subject | chromatin | en |
dc.subject | epigenetics | en |
dc.subject | stem cells | en |
dc.title | Genome-wide Mapping of Polycomb Target Genes Unravels Their Roles in Cell Fate Transitions. | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | European Commission | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/brackea | en |
dc.identifier.rssinternalid | 50040 | en |
dc.identifier.doi | http://dx.doi.org/10.1101/gad.381706 | en |
dc.subject.TCDTheme | Cancer | en |
dc.subject.TCDTheme | Genes & Society | en |
dc.identifier.orcid_id | 0000-0002-1547-9443 | en |