dc.contributor.author | Mendenhall, Eric M | |
dc.contributor.author | Koche, Richard Patrick | |
dc.contributor.author | Truong, Thanh | |
dc.contributor.author | Zhou, Vicky Weijie | |
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 | 2011-04-23T18:25:46Z | |
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 |
dc.identifier.doi | 10.1371/journal.pgen.1001244 | * |
dash.contributor.affiliated | Zhou, Vicky | |
dash.contributor.affiliated | Koche, Richard Patrick | |
dash.contributor.affiliated | Mendenhall, Eric M | |
dash.contributor.affiliated | Ku, Manching | |
dash.contributor.affiliated | Chi, Andrew S. | |
dash.contributor.affiliated | Bernstein, Bradley | |