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GC-rich sequence elements recruit PRC2 in mammalian ES cells
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نویسنده
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mendenhall e.m. ,koche r.p. ,truong t. ,zhou v.w. ,issac b. ,chi a.s. ,ku m. ,bernstein b.e.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 12 - صفحه:1 -10
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چکیده
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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. © 2010 mendenhall et al.
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آدرس
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howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma,united states,division of health sciences and technology,massachusetts institute of technology,cambridge,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma,united states,biological and biomedical sciences,harvard medical school,boston,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma,united states,neuro-oncology division,department of neurology,massachusetts general hospital,boston,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, howard hughes medical institute and department of pathology,massachusetts general hospital and harvard medical school,boston,ma,united states,center for systems biology and center for cancer research,massachusetts general hospital,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States
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Authors
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