GC-rich sequence elements recruit PRC2 in mammalian ES cells

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GC-rich sequence elements recruit PRC2 in mammalian ES cells

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dc.contributor.author Truong, Thanh
dc.contributor.author Issac, Biju
dc.contributor.author Mendenhall, Eric M
dc.contributor.author Koche, Richard Patrick
dc.contributor.author Zhou, Vicky Weijie
dc.contributor.author Chi, Andrew S.
dc.contributor.author Ku, Manching
dc.contributor.author Bernstein, Bradley E.
dc.date.accessioned 2011-04-23T18:25:46Z
dc.date.issued 2010
dc.identifier.citation Mendenhall, 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.issn 1553-7390 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874826
dc.description.abstract Polycomb 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.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pgen.1001244 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000368/pdf/ en_US
dash.license LAA
dc.subject developmental biology en_US
dc.subject cell differentiation en_US
dc.subject stem cells en_US
dc.subject genetics and genomics en_US
dc.subject epigenetics en_US
dc.subject gene expression en_US
dc.subject molecular biology en_US
dc.subject chromatin structure en_US
dc.subject histone modification en_US
dc.title GC-rich sequence elements recruit PRC2 in mammalian ES cells en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Genetics en_US
dash.depositing.author Mendenhall, Eric M
dc.date.available 2011-04-23T18:25:46Z
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Pathology en_US

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