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dc.contributor.authorEndoh, Mitsuhiro
dc.contributor.authorEndo, Takaho A.
dc.contributor.authorEndoh, Tamie
dc.contributor.authorIsono, Kyo-ichi
dc.contributor.authorSharif, Jafar
dc.contributor.authorOhara, Osamu
dc.contributor.authorToyoda, Tetsuro
dc.contributor.authorIto, Takashi
dc.contributor.authorEskeland, Ragnhild
dc.contributor.authorBickmore, Wendy A.
dc.contributor.authorKoseki, Haruhiko
dc.contributor.authorVidal, Miguel
dc.contributor.authorBernstein, Bradley E.
dc.date.accessioned2013-03-26T15:20:39Z
dc.date.issued2012
dc.identifier.citationEndoh, Mitsuhiro, Takaho A. Endo, Tamie Endoh, Kyo-ichi Isono, Jafar Sharif, Osamu Ohara, Tetsuro Toyoda, Takashi Ito, Ragnhild Eskeland, Wendy A. Bickmore, Miguel Vidal, Bradley E. Bernstein, and Haruhiko Koseki. 2012. Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity. PLoS Genetics 8(7): e1002774.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10464950
dc.description.abstractTwo distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3), respectively. Compared to H3K27me3, localization and the role of H2AK119u1 are not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002774en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405999/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectDevelopmental Biologyen_US
dc.subjectStem Cellsen_US
dc.subjectEmbryonic Stem Cellsen_US
dc.subjectCell Differentiationen_US
dc.subjectGeneticsen_US
dc.subjectEpigeneticsen_US
dc.subjectHistone Modificationen_US
dc.subjectChromatinen_US
dc.subjectGene Expressionen_US
dc.subjectMolecular Geneticsen_US
dc.subjectGene Regulationen_US
dc.subjectGenome-Wide Association Studiesen_US
dc.subjectGenomicsen_US
dc.subjectChromosome Biologyen_US
dc.subjectGenome Analysis Toolsen_US
dc.subjectMolecular Cell Biologyen_US
dc.titleHistone H2A Mono-Ubiquitination Is a Crucial Step to Mediate PRC1-Dependent Repression of Developmental Genes to Maintain ES Cell Identityen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorBernstein, Bradley E.
dc.date.available2013-03-26T15:20:39Z
dc.identifier.doi10.1371/journal.pgen.1002774*
dash.authorsorderedfalse
dash.contributor.affiliatedBernstein, Bradley


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