The Murine Polycomb Group Protein Eed Is Required for Global Histone H3 Lysine-27 Methylation
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PcG proteins mediate heritable transcriptional silencing by generating and recognizing covalent histone modifications. One conserved PcG complex, PRC2, is composed of several proteins including the histone methyltransferase (HMTase) Ezh2, the WD-repeat protein Eed, and the Zn-finger protein Suz12. Ezh2 methylates histone H3 on lysine 27 (H3K27), which serves as an epigenetic mark mediating silencing. H3K27 can be mono-, di-, or trimethylated (1mH3K27, 2mH3K27, and 3mH3K27, respectively). Hence, either PRC2 must be regulated so as to add one methyl group to certain nucleosomes but two or three to others, or distinct complexes must be responsible for 1m-, 2m-, and 3mH3K27. Consistent with the latter possibility, 2mH3K27 and 3mH3K27, but not 1mH3K27, are absent in Suz12-/- embryos, which lack both Suz12 and Ezh2 protein. Mammalian proteins required for 1mH3K27 have not been identified. Here, we demonstrate that unlike Suz12 and Ezh2, Eed is required not only for 2m- and 3mH3K27 but also global 1mH3K27. These results provide a functionally important distinction between PRC2 complex components and implicate Eed in PRC2-independent histone methylation.
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PRC2 inactivation was achieved by genetic ablation of EED, a core subunit of PRC2 essential for complex stability and catalytic activity.
“PRC2 inactivation was achieved by the genetic ablation of EED, a core subunit of PRC2, which is essential for complex stability and catalytic activity29.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [29]
Cites
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
The language of covalent histone modifications
Strahl, B. D., & Allis, C. D. (2000) · Nature · doi:10.1038/47412 · Cited by 8,679 · see citing works
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775 · see citing works
Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2002) · Genes & Development · doi:10.1101/gad.1035902 · Cited by 1,596 · see citing works
Histone Methyltransferase Activity of a Drosophila Polycomb Group Repressor Complex
Müller, J., Hart, C. M., Francis, N. J., Vargas, M. L., Sengupta, A. K., Wild, B., Miller, E., O’Connor, M. B., Kingston, R. E., & Simon, J. A. (2002) · Cell · doi:10.1016/s0092-8674(02)00976-5 · Cited by 1,553 · see citing works
Czermin, B., Melfi, R., McCabe, D., Seitz, V., Imhof, A., & Pirrotta, V. (2002) · Cell · doi:10.1016/s0092-8674(02)00975-3 · Cited by 1,536 · see citing works
Partitioning and Plasticity of Repressive Histone Methylation States in Mammalian Chromatin
Peters, A. H. F. M., Kubicek, S., Mechtler, K., O’Sullivan, R. J., Derijck, A. A. H. A., Perez-Burgos, L., Kohlmaier, A., Opravil, S., Tachibana, M., Shinkai, Y., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00477-5 · Cited by 1,148 · see citing works
Fischle, W., Wang, Y., Jacobs, S. A., Kim, Y., Allis, C. D., & Khorasanizadeh, S. (2003) · Genes & Development · doi:10.1101/gad.1110503 · Cited by 993 · see citing works
Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity
Pasini, D., Bracken, A. P., Jensen, M. R., Denchi, E. L., & Helin, K. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600402 · Cited by 910 · see citing works
Chromatin Compaction by a Polycomb Group Protein Complex
Francis, N. J., Kingston, R. E., & Woodcock, C. L. F. (2004) · Science · doi:10.1126/science.1100576 · Cited by 841 · see citing works
Silva, J., Mak, W., Zvetkova, I., Appanah, R., Nesterova, T. B., Webster, Z., Peters, A. H. F. M., Jenuwein, T., Otte, A. P., & Brockdorff, N. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00068-6 · Cited by 638 · see citing works
Self-citationvan der Vlag, J., & Otte, A. P. (1999) · Nature Genetics · doi:10.1038/70602 · Cited by 527 · see citing works
Self-citationPositional cloning of a global regulator of anterior–posterior patterning in mice
Schumacher, A., Faust, C. J., & Magnuson, T. (1996) · Nature · doi:10.1038/383250a0 · Cited by 292 · see citing works
Self-citationSu(var) genes regulate the balance between euchromatin and heterochromatin in DrosophilaPreprint
Ebert, A., Schotta, G., Lein, S., Kubicek, S., Krauß, V., Jenuwein, T., & Reuter, G. (2004) · Genes & Development · doi:10.1101/gad.323004 · Cited by 277 · see citing works
Sewalt, R. G. A. B., van der Vlag, J., Gunster, M. J., Hamer, K. M., den Blaauwen, J. L., Satijn, D. P. E., Hendrix, T., DRIEL, R. V., & Otte, A. P. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3586 · Cited by 221 · see citing works
Self-citationPoint Mutations in the WD40 Domain of Eed Block Its Interaction with Ezh2
Denisenko, O., Shnyreva, M., Suzuki, H., & Bomsztyk, K. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.10.5634 · Cited by 98 · see citing works
Denisenko, O. N., & Bomsztyk, K. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.8.4707 · Cited by 91 · see citing works
Dichtl, B., Aasland, R., & Keller, W. D. (2004) · RNA · doi:10.1261/rna.7090104 · Cited by 70 · see citing works
Erratum: Positional cloning of a global regulator of anterior–posterior patterning in mice
Schumacher, A., Faust, C., & Magnuson, T. (1996) · Nature · doi:10.1038/384648a0 · Cited by 67 · see citing works
Self-citationCell and tissue requirements for the gene eed during mouse gastrulation and organogenesis
Morin‐Kensicki, E., Faust, C. J., LaMantia, C., et al. (2001) · genesis · doi:10.1002/gene.10017 · Cited by 59 · see citing works
A Panel of Monoclonal Antibodies against Human Polycomb Group Proteins
Hamer, K. M., Sewalt, R. G. A. B., den Blaauwen, J. L., Hendrix, T., Satijn, D. P. E., & Otte, A. P. (2002) · Hybridoma and Hybridomics · doi:10.1089/153685902760213859 · Cited by 32 · see citing works
Self-citation
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Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895 · see citing works
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting
Schuettengruber, B., Bourbon, H.-M., Di Croce, L., & Cavalli, G. (2017) · Cell · doi:10.1016/j.cell.2017.08.002 · Cited by 1,094 · see citing works
Shen, X., Liu, Y., Hsu, Y.-J., Fujiwara, Y., Kim, J., Mao, X., Yuan, G.-C., & Orkin, S. H. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.016 · Cited by 1,021 · see citing works
Tan, J., Yang, X., Zhuang, L., Jiang, X., Chen, W., Lee, P. L., Karuturi, R. K. M., Tan, P. B. O., Liu, E. T., & Yu, Q. (2007) · Genes & Development · doi:10.1101/gad.1524107 · Cited by 895 · see citing works
Epigenetic regulation of brain region-specific microglia clearance activity
Ayata, P., Badimon, A., Strasburger, H. J., Duff, M. K., Montgomery, S. E., Loh, Y.-H. E., Ebert, A., Pimenova, A. A., Ramirez, B. R., Chan, A. T., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0192-3 · Cited by 460 · see citing works
Chromatin repressive complexes in stem cells, development, and cancer
Laugesen, A., & Helin, K. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.05.006 · Cited by 352 · see citing works
A key role for <i>EZH2</i> and associated genes in mouse and human adult T-cell acute leukemia
Simon, C., Chagraoui, J., Krosl, J., Gendron, P., Wilhelm, B., Lemieux, S., Boucher, G., Chagnon, P., Drouin, S., Lambert, R., et al. (2012) · Genes & Development · doi:10.1101/gad.186411.111 · Cited by 264 · see citing works
Mechanisms regulating PRC2 recruitment and enzymatic activity
Holoch, D., & Margueron, R. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.04.003 · Cited by 201 · see citing works
Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells
Jadhav, U., Nalapareddy, K., Saxena, M., O’Neill, N. K., Pinello, L., Yuan, G.-C., Orkin, S. H., & Shivdasani, R. A. (2016) · Cell · doi:10.1016/j.cell.2016.04.031 · Cited by 139 · see citing works
“PRC2 Loss In Vivo Impairs Cell Proliferation and Preferentially Activates Genes with Acquired TissueRestricted H3K27me3 To define this dependency, we disrupted Eed, a gene required for PRC2 assembly and catalytic activity (Montgomery et al., 2005).”
Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells
Majewski, I. J., Ritchie, M. E., Phipson, B., Corbin, J., Pakusch, M., Ebert, A., Busslinger, M., Koseki, H., Hu, Y., Smyth, G. K., et al. (2010) · Blood · doi:10.1182/blood-2009-12-260760 · Cited by 135 · see citing works
Smits, M., Mir, S. E., Nilsson, R. J. A., van der Stoop, P. M., Niers, J. M., Marquez, V. E., Cloos, J., Breakefield, X. O., Krichevsky, A. M., Noske, D. P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016282 · Cited by 118 · see citing works
Frequent deletions of <i>JARID2</i> in leukemic transformation of chronic myeloid malignancies
Puda, A., Milosevic, J. D., Berg, T., Klampfl, T., Harutyunyan, A. S., Gisslinger, B., Rumi, E., Pietra, D., Malcovati, L., Elena, C., et al. (2012) · American Journal of Hematology · doi:10.1002/ajh.22257 · Cited by 105 · see citing works
- Authors
- Montgomery, N. D., Yee, D., Chen, A., Kalantry, S., Chamberlain, S. J., Otte, A. P., & Magnuson, T.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Amsterdam (NL)
- Corresponding author
- Magnuson, Terry
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 15
- Issue
- 10
- Pages
- 942-947
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2110241629
- Cited by
- 345
- References
- 21
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 18 · 2021: 14 · 2020: 11 · 2019: 14 · 2018: 15 · 2017: 23 · 2016: 23 · 2015: 14 · 2014: 19 · 2013: 23 · 2012: 20
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3030 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UNC Libraries
- Funders
- American Cancer Society
- National Institutes of Health
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- EED, Polycomb group proteins, polycomb repressive complex 2, histone H3 lysine 27 methylation, H3K27me3, EZH2, SUZ12, transcriptional silencing, epigenetic inheritance, mouse embryo
- MeSH terms
- Animals, Cloning, Molecular, Embryo, Mammalian, Fluorescent Antibody Technique, Genetic Vectors, Histones, Lysine, Methylation, Repressor Proteins, Stem Cells, Blotting, Northern, Blotting, Western, Reverse Transcriptase Polymerase Chain Reaction, Gene Silencing, Epigenesis, Genetic, Mice, Polycomb Repressive Complex 2
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