GC-rich sequence elements recruit PRC2 in mammalian ES cells
| Title: | GC-rich sequence elements recruit PRC2 in mammalian ES cells |
| Author: |
Truong, Thanh; Issac, Biju; Mendenhall, Eric M; Koche, Richard Patrick; Zhou, Vicky Weijie; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
3000368.pdf (1.273Mb; PDF) 
|
| 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. |
| Published Version: | doi:10.1371/journal.pgen.1001244 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000368/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874826 |
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