The Polycomb complex PRC2 and its mark in life (original) (raw)

• Lewis, P. Pc: Polycomb. Drosoph. Inf. Ser. 21, 69 (1949).
  Google Scholar
• Lewis, E. B. A gene complex controlling segmentation in Drosophila . Nature 276, 565–570 (1978).
  Article ADS CAS PubMed Google Scholar
• Schuettengruber, B. & Cavalli, G. Recruitment of polycomb group complexes and their role in the dynamic regulation of cell fate choice. Development 136, 3531–3542 (2009).
  Article CAS PubMed Google Scholar
• Klymenko, T. et al. A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities. Genes Dev. 20, 1110–1122 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Scheuermann, J. C. et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465, 243–247 (2010).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Simon, J. A. & Kingston, R. E. Mechanisms of polycomb gene silencing: knowns and unknowns. Nature Rev. Mol. Cell Biol. 10, 697–708 (2009).
  Article CAS Google Scholar
• Eskeland, R. et al. Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol. Cell 38, 452–464 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Ku, M. et al. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet. 4, e1000242 (2008).
  Article PubMed PubMed Central CAS Google Scholar
• Sing, A. et al. A vertebrate Polycomb response element governs segmentation of the posterior hindbrain. Cell 138, 885–897 (2009).
  Article CAS PubMed Google Scholar
• Schoeftner, S. et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25, 3110–3122 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Whitcomb, S. J., Basu, A., Allis, C. D. & Bernstein, E. Polycomb Group proteins: an evolutionary perspective. Trends Genet. 23, 494–502 (2007).
  Article CAS PubMed Google Scholar
• Shaver, S., Casas-Mollano, J. A., Cerny, R. L. & Cerutti, H. Origin of the polycomb repressive complex 2 and gene silencing by an E(z) homolog in the unicellular alga Chlamydomonas . Epigenetics 5, 301–302 (2010).
  Article CAS PubMed Google Scholar
• Ohno, K., McCabe, D., Czermin, B., Imhof, A. & Pirrotta, V. ESC, ESCL and their roles in Polycomb Group mechanisms. Mech. Dev. 125, 527–541 (2008).
  Article CAS PubMed Google Scholar
• Margueron, R. et al. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol. Cell 32, 503–518 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Hennig, L. & Derkacheva, M. Diversity of Polycomb group complexes in plants: same rules, different players? Trends Genet. 25, 414–423 (2009).
  Article CAS PubMed Google Scholar
• Shen, X. et al. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol. Cell 32, 491–502 (2008).
  Article MathSciNet CAS PubMed PubMed Central Google Scholar
• Cao, R. & Zhang, Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED–EZH2 complex. Mol. Cell 15, 57–67 (2004).
  Article CAS PubMed Google Scholar
• Kim, H., Kang, K. & Kim, J. AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res. 37, 2940–2950 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, S., Robertson, G. P. & Zhu, J. A novel human homologue of Drosophila polycomblike gene is up-regulated in multiple cancers. Gene 343, 69–78 (2004).
  Article CAS PubMed Google Scholar
• Nekrasov, M. et al. Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes. EMBO J. 26, 4078–4088 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Walker, E. et al. Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation. Cell Stem Cell 6, 153–166 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Li, G. et al. Jarid2 and PRC2, partners in regulating gene expression. Genes Dev. 24, 368–380 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Sarma, K., Margueron, R., Ivanov, A., Pirrotta, V. & Reinberg, D. Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo . Mol. Cell. Biol. 28, 2718–2731 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Savla, U., Benes, J., Zhang, J. & Jones, R. S. Recruitment of Drosophila Polycomb-group proteins by Polycomblike, a component of a novel protein complex in larvae. Development 135, 813–817 (2008).
  Article CAS PubMed Google Scholar
• Jung, J., Mysliwiec, M. R. & Lee, Y. Roles of JUMONJI in mouse embryonic development. Dev. Dyn. 232, 21–32 (2005).
  Article CAS PubMed Google Scholar
• Peng, J. et al. Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 139, 1290–1302 (2009).
  Article PubMed PubMed Central Google Scholar
• Shen, X. et al. Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell 139, 1303–1314 (2009).
  Article PubMed PubMed Central Google Scholar
• Pasini, D. et al. JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 464, 306–310 (2010).
  Article ADS CAS PubMed Google Scholar
• Landeira, D. et al. Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Nature Cell Biol. 12, 618–624 (2010).
  Article CAS PubMed Google Scholar
• Zee, B. M. et al. In vivo residue-specific histone methylation dynamics. J. Biol. Chem. 285, 3341–3350 (2010).
  Article CAS PubMed Google Scholar
• Peters, A. H. et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12, 1577–1589 (2003).
  Article CAS PubMed Google Scholar
• Tie, F. et al. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136, 3131–3141 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Trojer, P. & Reinberg, D. Facultative heterochromatin: is there a distinctive molecular signature? Mol. Cell 28, 1–13 (2007).
  Article CAS PubMed Google Scholar
• Cui, K. et al. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell 4, 80–93 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Jacob, Y. et al. ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing. Nature Struct. Mol. Biol. 16, 763–768 (2009).
  Article CAS Google Scholar
• Pasini, D., Bracken, A. P., Hansen, J. B., Capillo, M. & Helin, K. The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol. Cell. Biol. 27, 3769–3779 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Swigut, T. & Wysocka, J. H3K27 demethylases, at long last. Cell 131, 29–32 (2007).
  Article CAS PubMed Google Scholar
• Barski, A. et al. High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837 (2007).
  Article CAS PubMed Google Scholar
• Mikkelsen, T. S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560 (2007).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Stock, J. K. et al. Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nature Cell Biol. 9, 1428–1435 (2007).
  Article CAS PubMed Google Scholar
• Zhao, X. D. et al. Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell 1, 286–298 (2007).
  Article CAS PubMed Google Scholar
• Kanhere, A. et al. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol. Cell 38, 675–688 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Mohn, F. et al. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol. Cell 30, 755–766 (2008). This paper compares genome enrichment of H3K27me3, H3K4me3 and DNA methylation in ES cells with that in terminally differentiated neurons, demonstrating the plasticity of these marks.
  Article CAS PubMed Google Scholar
• Lee, T. I. et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125, 301–313 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Boyer, L. A. et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349–353 (2006).
  Article ADS CAS PubMed Google Scholar
• Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H. & Helin, K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 20, 1123–1136 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Squazzo, S. L. et al. Suz12 binds to silenced regions of the genome in a cell-type-specific manner. Genome Res. 16, 890–900 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Schwartz, Y. B. et al. Genome-wide analysis of Polycomb targets in Drosophila melanogaster . Nature Genet. 38, 700–705 (2006).
  Article CAS PubMed Google Scholar
• Tolhuis, B. et al. Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster . Nature Genet. 38, 694–699 (2006).
  Article CAS PubMed Google Scholar
• Hawkins, R. D. et al. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6, 479–491 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Pan, G. et al. Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1, 299–312 (2007).
  Article CAS PubMed Google Scholar
• Rosenfeld, J. A. et al. Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genomics 10, 143 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Leeb, M. et al. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev. 24, 265–276 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Margueron, R. & Reinberg, D. Chromatin structure and the inheritance of epigenetic information. Nature Rev. Genet. 11, 285–296 (2010).
  Article CAS PubMed Google Scholar
• Mattout, A. & Meshorer, E. Chromatin plasticity and genome organization in pluripotent embryonic stem cells. Curr. Opin. Cell Biol. 22, 334–341 (2010).
  Article CAS PubMed Google Scholar
• Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).
  Article CAS PubMed Google Scholar
• Vastenhouw, N. L. et al. Chromatin signature of embryonic pluripotency is established during genome activation. Nature 464, 922–926 (2010).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Schuettengruber, B. et al. Functional anatomy of polycomb and trithorax chromatin landscapes in Drosophila embryos. PLoS Biol. 7, e13 (2009).
  Article PubMed CAS Google Scholar
• Creyghton, M. P. et al. H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135, 649–661 (2008). This paper reports co-localization of the histone variant H2Az with PRC2 in undifferentiated ES cells, illustrating changes in chromatin structure while cells differentiate.
  Article CAS PubMed PubMed Central Google Scholar
• Meissner, A. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766–770 (2008).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Brunner, A. L. et al. Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver. Genome Res. 19, 1044–1056 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Zemach, A., McDaniel, I. E., Silva, P. & Zilberman, D. Genome-wide evolutionary analysis of eukaryotic DNA methylation. Science 328, 916–919 (2010).
  Article ADS CAS PubMed Google Scholar
• Woo, C. J., Kharchenko, P. V., Daheron, L., Park, P. J. & Kingston, R. E. A region of the human HOXD cluster that confers polycomb-group responsiveness. Cell 140, 99–110 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Wilkinson, F. H., Park, K. & Atchison, M. L. Polycomb recruitment to DNA in vivo by the YY1 REPO domain. Proc. Natl Acad. Sci. USA 103, 19296–19301 (2006).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Xi, H. et al. Analysis of overrepresented motifs in human core promoters reveals dual regulatory roles of YY1. Genome Res. 17, 798–806 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–135 (2003).
  Article ADS CAS PubMed Google Scholar
• Maenner, S. et al. 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol. 8, e1000276 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Zhao, J., Sun, B. K., Erwin, J. A., Song, J. J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322, 750–756 (2008).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Kohlmaier, A. et al. A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol. 2, E171 (2004).
  Article PubMed PubMed Central Google Scholar
• Pandey, R. R. et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol. Cell 32, 232–246 (2008).
  Article CAS PubMed Google Scholar
• Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311–1323 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Tsai, M. C. et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329, 689–693 (2010). This paper shows a widespread role for HOTAIR ncRNA in the regulation of PRC2 gene targeting, and suggests that HOTAIR bridges PRC2 and LSD1.
  Article ADS CAS PubMed PubMed Central Google Scholar
• Khalil, A. M. et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc. Natl Acad. Sci. USA 106, 11667–11672 (2009).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Song, J. J., Garlick, J. D. & Kingston, R. E. Structural basis of histone H4 recognition by p55. Genes Dev. 22, 1313–1318 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Margueron, R. et al. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461, 762–767 (2009). This paper reports that PRC2 function is regulated by the mark it deposits, thus providing a potential mechanism for the spreading of this mark.
  Article ADS CAS PubMed PubMed Central Google Scholar
• Chen, S. et al. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nature Cell Biol. 12, 1108–1114 (2010).
  Article CAS PubMed Google Scholar
• Kaneko, S. et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and upregulates its binding to HOTAIR ncRNA. Genes Dev. 24, 2615–2620 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Yap, K. L. et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a . Mol. Cell 38, 662–674 (2010). In this paper, the authors suggested that ncRNA and H3K27me3 can work together to contribute to PRC1 recruitment.
  Article CAS PubMed PubMed Central Google Scholar
• Francis, N. J., Follmer, N. E., Simon, M. D., Aghia, G. & Butler, J. D. Polycomb proteins remain bound to chromatin and DNA during DNA replication in vitro . Cell 137, 110–122 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hansen, K. H. et al. A model for transmission of the H3K27me3 epigenetic mark. Nature Cell Biol. 10, 1291–1300 (2008).
  Article CAS PubMed Google Scholar
• Chamberlain, S. J., Yee, D. & Magnuson, T. Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency. Stem Cells 26, 1496–1505 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Yuzyuk, T., Fakhouri, T. H., Kiefer, J. & Mango, S. E. The polycomb complex protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos. Dev. Cell 16, 699–710 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Endoh, M. et al. Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. Development 135, 1513–1524 (2008).
  Article CAS PubMed Google Scholar
• Su, I. H. et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nature Immunol. 4, 124–131 (2003).
  Article CAS Google Scholar
• Wang, L., Jin, Q., Lee, J. E., Su, I. H. & Ge, K. Histone H3K27 methyltransferase Ezh2 represses Wnt genes to facilitate adipogenesis. Proc. Natl Acad. Sci. USA 107, 7317–7322 (2010).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Caretti, G., Di Padova, M., Micales, B., Lyons, G. E. & Sartorelli, V. The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev. 18, 2627–2638 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Ezhkova, E. et al. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 136, 1122–1135 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Varambally, S. et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624–629 (2002).
  Article ADS CAS PubMed Google Scholar
• Kleer, C. G. et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl Acad. Sci. USA 100, 11606–11611 (2003).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Karanikolas, B. D., Figueiredo, M. L. & Wu, L. Polycomb group protein enhancer of zeste 2 is an oncogene that promotes the neoplastic transformation of a benign prostatic epithelial cell line. Mol. Cancer Res. 7, 1456–1465 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Li, X. et al. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia. Am. J. Pathol. 175, 1246–1254 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Bracken, A. P. et al. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 22, 5323–5335 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Bracken, A. P. et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 21, 525–530 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Morin, R. D. et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nature Genet. 42, 181–185 (2010). This study is the first report that somatic mutations resulting in the inactivation of PRC2 are found in diseases.
  Article CAS PubMed Google Scholar
• Ernst, T. et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nature Genet. 42, 722–726 (2010).
  Article CAS PubMed Google Scholar
• Nikoloski, G. et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nature Genet. 42, 665–667 (2010).
  Article CAS PubMed Google Scholar
• Karanikolas, B. D., Figueiredo, M. L. & Wu, L. Comprehensive evaluation of the role of EZH2 in the growth, invasion, and aggression of a panel of prostate cancer cell lines. Prostate 70, 675–688 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Pereira, C. F., Piccolo, F. M., Tsubouchi, T., Sauer, S. & Ryan, N. ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency. Cell Stem Cell 6, 547–556 (2010).
  Article CAS PubMed Google Scholar