GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells
Author(s)Mendenhall, Eric M.; Koche, Richard Patrick; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.; ... Show more Show less
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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.
DepartmentHarvard University--MIT Division of Health Sciences and Technology
Public Library of Science
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.
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