dc.contributor.author | Mendenhall, Eric M. | |
dc.contributor.author | Koche, Richard Patrick | |
dc.contributor.author | Truong, Thanh | |
dc.contributor.author | Zhou, Vicky W. | |
dc.contributor.author | Issac, Biju | |
dc.contributor.author | Chi, Andrew S. | |
dc.contributor.author | Ku, Manching | |
dc.contributor.author | Bernstein, Bradley E. | |
dc.date.accessioned | 2011-07-14T17:01:46Z | |
dc.date.available | 2011-07-14T17:01:46Z | |
dc.date.issued | 2010-12 | |
dc.date.submitted | 2010-06 | |
dc.identifier.issn | 1553-7404 | |
dc.identifier.issn | 1553-7390 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/64809 | |
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.description.sponsorship | Burroughs Wellcome Fund | en_US |
dc.description.sponsorship | Charles E. Culpeper Foundation | en_US |
dc.description.sponsorship | Massachusetts General Hospital | en_US |
dc.description.sponsorship | Broad Institute of MIT and Harvard | en_US |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pgen.1001244 | en_US |
dc.rights | Creative Commons Attribution | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en_US |
dc.source | PLoS | en_US |
dc.title | GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Mendenhall, 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.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.approver | Koche, Richard Patrick | |
dc.contributor.mitauthor | Koche, Richard Patrick | |
dc.relation.journal | PLoS Genetics | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E. | en |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |