2010 Fiscal Year Final Research Report
Dissecting molecular mechanisms mediated by Polycomb group proteins in maintenance and differentiation of ES cells
| Project/Area Number |
20390088
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
KOSEKI HARUHIKO The Institute of Physical and Chemical Research, 免疫器官形成研究グループ, グループディレクター (40225446)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAHO Endoh 独立行政法人理化学研究所, 生命情報基盤研究部門, 研究員 (40384862)
MITSUHIRO Endoh 独立行政法人理化学研究所, 免疫器官形成研究グループ, 研究員 (40391883)
JUN Shinga 独立行政法人理化学研究所, 免疫器官形成研究グループ, 研究員 (20334211)
FUJIMURA Yu-Ichi 独立行政法人理化学研究所, 免疫器官形成研究グループ, 研究員 (60392099)
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| Project Period (FY) |
2008 – 2010
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| Research Abstract |
Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). Although the respective complexes catalyze mono-ubiquitination of histone H2A (H2Aub1) and trimethylation of H3 lysine 27 (H3K27me3), the extent which these modifications contribute to Polycomb repression remains controversial. To address this issue, we characterized PRC1 mutants that either lack the ability to catalyze H2Aub1 or ineffectively bind H3K27me3. We find that the catalytically-inactive PRC1 mutant maintains the ability to compact chromatin at the Hox loci, but is nonetheless essential to facilitate repression of target genes and to maintain ESCs in an undifferentiated state. We further show that PRC1 localization and H2Aub1 deposition at most but not all target loci depends on physical recognition of H3K27me3 by CBX2, a core PRC1 subunit. Our data suggest that heterogeneous mechanisms, including chromatin compaction and ubiquitination, as well as PRC2-dependent and PRC2-independent recruitment modes underlie PRC1 function. Such diverse sensing mechanisms and effectors might be required for appropriate loading of PRC1 onto heterogeneous target loci, and/or to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.
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[Journal Article] Mammalian Polycomblike Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate Polycomb activity at both the Hox gene cluster and at Cdkn2a genes2011
Author(s)
Li X, Isono KI, Yamada D, Endo TA, Endoh M, Shinga J, Mizutani-Koseki Y, Otte AP, Casanova M, Kitamura H, Kamijo T, Sharif J, Ohara O, Toyada T, Bernstein BE, Brockdorff N, Koseki H
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Journal Title
Peer Reviewed
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[Journal Article] ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency2010
Author(s)
Pereira CF, Piccolo FM, Tsubouchi T, Sauer S, Ryan NK, Bruno L, Landeira D, Santos J, Banito A, Gil J, Koseki H, Merkenschlager M, Fisher AG
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Journal Title
Cell Stem Cell. 6
Pages: 547-556
Peer Reviewed
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[Journal Article] Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains2008
Author(s)
Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE
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Journal Title
PLoS Genet. 4
Pages: e1000242
Peer Reviewed
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[Journal Article] Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity2008
Author(s)
Endoh M., Endo T.A., Endoh T., Fujimura Y., Ohara O., Toyoda T., Otte A.P., Okano M., Brockdorff N., Vidal M., Koseki H.
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Journal Title
Development 135
Pages: 1513-1524
Peer Reviewed
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