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dc.contributor.authorMendenhall, Eric M
dc.contributor.authorKoche, Richard Patrick
dc.contributor.authorTruong, Thanh
dc.contributor.authorZhou, Vicky Weijie
dc.contributor.authorIssac, Biju
dc.contributor.authorChi, Andrew S.
dc.contributor.authorKu, Manching
dc.contributor.authorBernstein, Bradley E.
dc.date.accessioned2011-04-23T18:25:46Z
dc.date.issued2010
dc.identifier.citationMendenhall, Eric M., Richard P. Koche, Thanh Truong, Vicky W. Zhou, Biju Issac, Andrew S. Chi, Manching Ku, and Bradley E. Bernstein. 2010. GC-rich sequence elements recruit PRC2 in mammalian ES cells. PLoS Genetics 6(12): e1001244.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4874826
dc.description.abstractPolycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1001244en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000368/pdf/en_US
dash.licenseLAA
dc.subjectdevelopmental biologyen_US
dc.subjectcell differentiationen_US
dc.subjectstem cellsen_US
dc.subjectgenetics and genomicsen_US
dc.subjectepigeneticsen_US
dc.subjectgene expressionen_US
dc.subjectmolecular biologyen_US
dc.subjectchromatin structureen_US
dc.subjecthistone modificationen_US
dc.titleGC-rich sequence elements recruit PRC2 in mammalian ES cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorMendenhall, Eric M
dc.date.available2011-04-23T18:25:46Z
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Pathologyen_US
dc.identifier.doi10.1371/journal.pgen.1001244*
dash.contributor.affiliatedZhou, Vicky
dash.contributor.affiliatedKoche, Richard Patrick
dash.contributor.affiliatedMendenhall, Eric M
dash.contributor.affiliatedKu, Manching
dash.contributor.affiliatedChi, Andrew S.
dash.contributor.affiliatedBernstein, Bradley


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