GC-rich sequence elements recruit PRC2 in mammalian ES cells

GC-rich sequence elements recruit PRC2 in mammalian ES cells

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GC-rich sequence elements recruit PRC2 in mammalian ES cells

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