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dc.contributor.authorMendenhall, Eric M.
dc.contributor.authorKoche, Richard Patrick
dc.contributor.authorTruong, Thanh
dc.contributor.authorZhou, Vicky W.
dc.contributor.authorIssac, Biju
dc.contributor.authorChi, Andrew S.
dc.contributor.authorKu, Manching
dc.contributor.authorBernstein, Bradley E.
dc.date.accessioned2011-07-14T17:01:46Z
dc.date.available2011-07-14T17:01:46Z
dc.date.issued2010-12
dc.date.submitted2010-06
dc.identifier.issn1553-7404
dc.identifier.issn1553-7390
dc.identifier.urihttp://hdl.handle.net/1721.1/64809
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.description.sponsorshipBurroughs Wellcome Funden_US
dc.description.sponsorshipCharles E. Culpeper Foundationen_US
dc.description.sponsorshipMassachusetts General Hospitalen_US
dc.description.sponsorshipBroad Institute of MIT and Harvarden_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pgen.1001244en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en_US
dc.sourcePLoSen_US
dc.titleGC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cellsen_US
dc.typeArticleen_US
dc.identifier.citationMendenhall, Eric M. et al. “GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells.” Ed. Hiten D. Madhani. PLoS Genetics 6.12 (2010) : e1001244. Copyright: © 2010 Mendenhall et al.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.approverKoche, Richard Patrick
dc.contributor.mitauthorKoche, Richard Patrick
dc.relation.journalPLoS Geneticsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsMendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.en
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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