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Vol. 185, No. 1-3, 2007
Issue release date: June 2007
Cells Tissues Organs 2007;185:162–174
(DOI:10.1159/000101317)

Chromatin Structure Regulation in Transforming Growth Factor-β-Directed Epithelial-Mesenchymal Transition

Blumenberg M. · Gao S. · Dickman K. · Grollman A.P. · Bottinger E.P. · Zavadil J.
aDepartment of Dermatology, New York University School of Medicine, bDepartment of Pharmacological Sciences, SUNY Stony Brook, cDepartment of Medicine, VA Medical Center, Northport, dDepartment of Medicine, Mount Sinai Medical Center, and eDepartment of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, N.Y., USA

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Abstract

Epithelial-mesenchymal transitions (EMTs) occur in organogenesis throughout embryonic development and are recapitulated during epithelial tissue injury and in carcinoma progression. EMTs are regulated by complex, precisely orchestrated cell signaling and gene expression networks, with the participation of key developmental pathways. Here we review context-dependent modules of gene regulation by hairy/enhancer-of-split-related (H/E(spl)) repressors downstream of transforming growth factor-β (TGF-β)/Smad and Notch signals in EMT and in other phenotype transitions such as differentiation and cancer. Based on multiple models of disease-related EMT, we propose that Polycomb group epigenetic silencers and histone-lysine methyl-transferases EZH1 and EZH2 are candidate targets of H/E(spl)-mediated transcriptional repression, in a process accompanied by replacement of modified core histone H3 with de novo synthesized histone variant H3.3B. Finally, we discuss the potential significance of this scenario for EMT in the light of recent findings on gene regulation by histone modifications and chromatin structure changes.



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References

  1. Abel, K.J., L.C. Brody, J.M. Valdes, M.R. Erdos, D.R. McKinley, L.H. Castilla, S.D. Merajver, F.J. Couch, L.S. Friedman, E.A. Ostermeyer, E.D. Lynch, M.C. King, P.L. Welcsh, S. Osborne-Lawrence, M. Spillman, A.M. Bowcock, F.S. Collins, B.L. Weber (1996) Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1. Genomics 37: 161–171.
  2. Ader, T., R. Norel, L. Levoci, L.E. Rogler (2006) Transcriptional profiling implicates TGFbeta/BMP and Notch signaling pathways in ductular differentiation of fetal murine hepatoblasts. Mech Dev 123: 177–194.
  3. Ahmad, K., S. Henikoff (2002) The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 9: 1191–1200.
  4. Ahmed, S., A. Nawshad (2007) Complexity in interpretation of embryonic epithelial-mesenchymal transformation in response to transforming growth factor-β signaling. Cells Tissues Organs 185: 131–145.
  5. Akhurst, R.J., R. Derynck (2001) TGF-beta signaling in cancer – a double-edged sword. Trends Cell Biol 11: S44–51.
  6. Albig, W., B. Bramlage, K. Gruber, H.G. Klobeck, J. Kunz, D. Doenecke (1995) The human replacement histone H3.3B gene (H3F3B). Genomics 30: 264–272.
  7. Axelson, H. (2004) Notch signaling and cancer: emerging complexity. Semin Cancer Biol 14: 317–319.
  8. Bachmann, I.M., O.J. Halvorsen, K. Collett, I.M. Stefansson, O. Straume, S.A. Haukaas, H.B. Salvesen, A.P. Otte, L.A. Akslen (2006) EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 24: 268–273.
  9. Bannister, A.J., R. Schneider, T. Kouzarides (2002) Histone methylation: dynamic or static? Cell 109: 801–806.
  10. Bates, R.C., A.M. Mercurio (2005) The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther 4: 365–370
  11. Bessho, Y., R. Kageyama (2003) Oscillations, clocks and segmentation. Curr Opin Genet Dev 13: 379–384.
  12. Blander, G., L. Guarente (2004) The Sir2 family of protein deacetylases. Annu Rev Biochem 73: 417–435.
  13. Blokzijl, A., C. Dahlqvist, E. Reissmann, A. Falk, A. Moliner, U. Lendahl, C.F. Ibanez (2003) Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J Cell Biol 163: 723–728.
  14. Boyer, L.A., K. Plath, J. Zeitlinger, T. Brambrink, L.A. Medeiros, T.I. Lee, S.S. Levine, M. Wernig, A. Tajonar, M.K. Ray, G.W. Bell, A.P. Otte, M. Vidal, D.K. Gifford, R.A. Young, R. Jaenisch (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441: 349–353.
  15. Bracken, A.P., N. Dietrich, D. Pasini, K.H. Hansen, K. Helin (2006) Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 20: 1123–1136.
  16. Bracken, A.P., D. Pasini, M. Capra, E. Prosperini, E. Colli, K. Helin (2003) EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 22: 5323–5335.
  17. Bramlage, B., U. Kosciessa, D. Doenecke (1997) Differential expression of the murine histone genes H3.3A and H3.3B. Differentiation 62: 13–20.
  18. Brock, H.W., C.L. Fisher (2005) Maintenance of gene expression patterns. Dev Dyn 232: 633–655.
  19. Cao, R., L. Wang, H. Wang, L. Xia, H. Erdjument-Bromage, P. Tempst, R.S. Jones, Y. Zhang (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298: 1039–1043.
  20. Cao, R., Y. Zhang (2004) The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 14: 155–164.
  21. Caretti, G., M. Di Padova, B. Micales, G.E. Lyons, V. Sartorelli (2004) The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev 18: 2627–2638.
  22. Cha, T.L., B.P. Zhou, W. Xia, Y. Wu, C.C. Yang, C.T. Chen, B. Ping, A.P. Otte, M.C. Hung (2005) Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 310: 306–310.
  23. Chen, X., M. Hiller, Y. Sancak, M.T. Fuller (2005) Tissue-specific TAFs counteract Polycomb to turn on terminal differentiation. Science 310: 869–872.
  24. Chin, M.T., K. Maemura, S. Fukumoto, M.K. Jain, M.D. Layne, M. Watanabe, C.M. Hsieh, M.E. Lee (2000) Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. J Biol Chem 275: 6381–6387.
  25. Chow, C.M., A. Georgiou, H. Szutorisz, A. Maia e Silva, A. Pombo, I. Barahona, E. Dargelos, C. Canzonetta, N. Dillon (2005) Variant histone H3.3 marks promoters of transcriptionally active genes during mammalian cell division. EMBO Rep 6: 354–360.
  26. Cossins, J., A.E. Vernon, Y. Zhang, A. Philpott, P.H. Jones (2002) Hes6 regulates myogenic differentiation. Development 129: 2195–2207.
  27. Cui, W., D.J. Fowlis, S. Bryson, E. Duffie, H. Ireland, A. Balmain, R.J. Akhurst (1996) TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 86: 531–542.
  28. Cuthbert, G.L., S. Daujat, A.W. Snowden, H. Erdjument-Bromage, T. Hagiwara, M. Yamada, R. Schneider, P.D. Gregory, P. Tempst, A.J. Bannister, T. Kouzarides (2004) Histone deimination antagonizes arginine methylation. Cell 118: 545–553.
  29. Czermin, B., R. Melfi, D. McCabe, V. Seitz, A. Imhof, V. Pirrotta (2002) Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111: 185–196.
  30. Davis, R.L., D.L. Turner (2001) Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning. Oncogene 20: 8342–8357.
  31. Dellino, G.I., Y.B. Schwartz, G. Farkas, D. McCabe, S.C. Elgin, V. Pirrotta (2004) Polycomb silencing blocks transcription initiation. Mol Cell 13: 887–893.
  32. Derynck, R., R.J. Akhurst, A. Balmain (2001) TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29: 117–129.
  33. Erhardt, S., I.H. Su, R. Schneider, S. Barton, A.J. Bannister, L. Perez-Burgos, T. Jenuwein, T. Kouzarides, A. Tarakhovsky, M.A. Surani (2003) Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development. Development 130: 4235–4248.
  34. Faust, C., A. Schumacher, B. Holdener, T. Magnuson (1995) The eed mutation disrupts anterior mesoderm production in mice. Development 121: 273–285.
  35. Francis, N.J., R.E. Kingston, C.L. Woodcock (2004) Chromatin compaction by a polycomb group protein complex. Science 306: 1574–1577.
  36. Frank, D., D. Doenecke, W. Albig (2003) Differential expression of human replacement and cell cycle dependent H3 histone genes. Gene 312: 135–143.
  37. Frazer, K.A., L. Pachter, A. Poliakov, E.M. Rubin, I. Dubchak (2004) VISTA: computational tools for comparative genomics. Nucleic Acids Res 32: W273–279.
  38. Gao, X., T. Chandra, M.O. Gratton, I. Quelo, J. Prud’homme, S. Stifani, R. St-Arnaud (2001) HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. J Cell Biol 154: 1161–1171.
  39. Gessler, M., K.P. Knobeloch, A. Helisch, K. Amann, N. Schumacher, E. Rohde, A. Fischer, C. Leimeister (2002) Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac defects in Hey2 –/– mice. Curr Biol 12: 1601–1604.
  40. Giudicelli, F., J. Lewis (2004) The vertebrate segmentation clock. Curr Opin Genet Dev 14: 407–414.
  41. Grego-Bessa, J., J. Diez, L. Timmerman, J.L. de la Pompa (2004) Notch and epithelial-mesenchyme transition in development and tumor progression: another turn of the screw. Cell Cycle 3: 718–721.
  42. Grove, G.W., A. Zweidler (1984) Regulation of nucleosomal core histone variant levels in differentiating murine erythroleukemia cells. Biochemistry 23: 4436–4443.
  43. Han, G., S.L. Lu, A.G. Li, W. He, C.L. Corless, M. Kulesz-Martin, X.J. Wang (2005) Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest 115: 1714–1723.
  44. Hay, E.D. (2005) The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn 233: 706–720.
  45. Hirata, H., S. Yoshiura, T. Ohtsuka, Y. Bessho, T. Harada, K. Yoshikawa, R. Kageyama (2002) Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science 298: 840–843.
  46. Hobert, O., B. Jallal, A. Ullrich (1996a) Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression. Mol Cell Biol 16: 3066–3073.
  47. Hobert, O., I. Sures, T. Ciossek, M. Fuchs, A. Ullrich (1996b) Isolation and developmental expression analysis of Enx-1, a novel mouse Polycomb group gene. Mech Dev 55: 171–184.
  48. Hraba-Renevey, S., M. Kress (1989) Expression of a mouse replacement histone H3.3 gene with a highly conserved 3′ noncoding region during SV40- and polyoma-induced Go to S-phase transition. Nucleic Acids Res 17: 2449–2461.
  49. Huang, Y., J. Fang, M.T. Bedford, Y. Zhang, R.M. Xu (2006) Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A. Science 312: 748–751.
  50. Huber, M.A., N. Kraut, H. Beug (2005) Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17: 548–558.
  51. Iso, T., L. Kedes, Y. Hamamori (2003) HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194: 237–255.
  52. Itoh, F., S. Itoh, M.J. Goumans, G. Valdimarsdottir, T. Iso, G.P. Dotto, Y. Hamamori, L. Kedes, M. Kato, P. Dijke Pt (2004) Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells. EMBO J 23: 541–551.
  53. Janicki, S.M., T. Tsukamoto, S.E. Salghetti, W.P. Tansey, R. Sachidanandam, K.V. Prasanth, T. Ried, Y. Shav-Tal, E. Bertrand, R.H. Singer, D.L. Spector (2004) From silencing to gene expression: real-time analysis in single cells. Cell 116: 683–698.
  54. Jenuwein, T., C.D. Allis (2001) Translating the histone code. Science 293: 1074–1080.
  55. John, G.R., S.L. Shankar, B. Shafit-Zagardo, A. Massimi, S.C. Lee, C.S. Raine, C.F. Brosnan (2002) Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 8: 1115–1121.
  56. Jouve, C., I. Palmeirim, D. Henrique, J. Beckers, A. Gossler, D. Ish-Horowicz, O. Pourquie (2000) Notch signalling is required for cyclic expression of the hairy-like gene HES1 in the presomitic mesoderm. Development 127: 1421–1429.
  57. Kalluri, R., E.G. Neilson (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 112: 1776–1784.
  58. Kamminga, L.M., L.V. Bystrykh, A. de Boer, S. Houwer, J. Douma, E. Weersing, B. Dontje, G. de Haan (2006) The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 107: 2170–2179.
  59. Kent, W.J., C.W. Sugnet, T.S. Furey, K.M. Roskin, T.H. Pringle, A.M. Zahler, D. Haussler (2002) The human genome browser at UCSC. Genome Res 12: 996–1006.
  60. Kirmizis, A., S.M. Bartley, P.J. Farnham (2003) Identification of the polycomb group protein SU(Z)12 as a potential molecular target for human cancer therapy. Mol Cancer Ther 2: 113–121.
  61. Kirmizis, A., S.M. Bartley, A. Kuzmichev, R. Margueron, D. Reinberg, R. Green, P.J. Farnham (2004) Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev 18: 1592–1605.
  62. Kleer, C.G., Q. Cao, S. Varambally, R. Shen, I. Ota, S.A. Tomlins, D. Ghosh, R.G. Sewalt, A.P. Otte, D.F. Hayes, M.S. Sabel, D. Livant, S.J. Weiss, M.A. Rubin, A.M. Chinnaiyan (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100: 11606–11611.
  63. Krimer, D.B., G. Cheng, A.I. Skoultchi (1993) Induction of H3.3 replacement histone mRNAs during the precommitment period of murine erythroleukemia cell differentiation. Nucleic Acids Res 21: 2873–2879.
  64. Kuroda, K., S. Tani, K. Tamura, S. Minoguchi, H. Kurooka, T. Honjo (1999) Delta-induced Notch signaling mediated by RBP-J inhibits MyoD expression and myogenesis. J Biol Chem 274: 7238–7244.
  65. Kuzmichev, A., T. Jenuwein, P. Tempst, D. Reinberg (2004) Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell 14: 183–193.
  66. Kuzmichev, A., K. Nishioka, H. Erdjument-Bromage, P. Tempst, D. Reinberg (2002) Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev 16: 2893–2905.
  67. Laible, G., A. Wolf, R. Dorn, G. Reuter, C. Nislow, A. Lebersorger, D. Popkin, L. Pillus, T. Jenuwein (1997) Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres. EMBO J 16: 3219–3232.
  68. Larue, L., A. Bellacosa (2005) Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene 24: 7443–7454.
  69. Lee, J.M., S. Dedhar, R. Kalluri, E.W. Thompson (2006) The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172: 973–981.
  70. Lee, T.I., R.G. Jenner, L.A. Boyer, M.G. Guenther, S.S. Levine, R.M. Kumar, B. Chevalier, S.E. Johnstone, M.F. Cole, K. Isono, H. Koseki, T. Fuchikami, K. Abe, H.L. Murray, J.P. Zucker, B. Yuan, G.W. Bell, E. Herbolsheimer, N.M. Hannett, K. Sun, D.T. Odom, A.P. Otte, T.L. Volkert, D.P. Bartel, D.A. Melton, D.K. Gifford, R. Jaenisch, R.A. Young (2006) Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125: 301–313.
  71. Lefort, K., G.P. Dotto (2004) Notch signaling in the integrated control of keratinocyte growth/differentiation and tumor suppression. Semin Cancer Biol 14: 374–386.
  72. Levine, S.S., I.F. King, R.E. Kingston (2004) Division of labor in polycomb group repression. Trends Biochem Sci 29: 478–485.
  73. Li, H., E.P. Nord (2002) CD40 ligation stimulates MCP-1 and IL-8 production, TRAF6 recruitment, and MAPK activation in proximal tubule cells. Am J Physiol Renal Physiol 282: F1020–F1033.
  74. Liu, Y. (2004) Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 15: 1–12.
  75. Maillard, I., W.S. Pear (2003) Notch and cancer: best to avoid the ups and downs. Cancer Cell 3: 203–205.
  76. Marx, J. (2005) Developmental biology. Combing over the Polycomb group proteins. Science 308: 624–626.
  77. Masuda, S., K. Kumano, K. Shimizu, Y. Imai, M. Kurokawa, S. Ogawa, M. Miyagishi, K. Taira, H. Hirai, S. Chiba (2005) Notch1 oncoprotein antagonizes TGF-beta/Smad-mediated cell growth suppression via sequestration of coactivator p300. Cancer Sci 96: 274–282.
  78. McKittrick, E., P.R. Gafken, K. Ahmad, S. Henikoff (2004) Histone H3.3 is enriched in covalent modifications associated with active chromatin. Proc Natl Acad Sci USA 101: 1525–1530.
  79. Metzger, E., M. Wissmann, N. Yin, J.M. Muller, R. Schneider, A.H. Peters, T. Gunther, R. Buettner, R. Schule (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437: 436–439.
  80. Miele, L. (2006) Notch signaling. Clin Cancer Res 12: 1074–1079.
  81. Minucci, S., P.G. Pelicci (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6: 38–51.
  82. Mito, Y., J.G. Henikoff, S. Henikoff (2005) Genome-scale profiling of histone H3.3 replacement patterns. Nat Genet 37: 1090–1097.
  83. Morrissey, J., G. Guo, K. Moridaira, M. Fitzgerald, R. McCracken, T. Tolley, S. Klahr (2002) Transforming growth factor-beta induces renal epithelial jagged-1 expression in fibrotic disease. J Am Soc Nephrol 13: 1499–1508.
  84. Muller, J., C.M. Hart, N.J. Francis, M.L. Vargas, A. Sengupta, B. Wild, E.L. Miller, M.B. O’Connor, R.E. Kingston, J.A. Simon (2002) Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111: 197–208.
  85. Nicolas, M., A. Wolfer, K. Raj, J.A. Kummer, P. Mill, M. van Noort, C.C. Hui, H. Clevers, G.P. Dotto, F. Radtke (2003) Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33: 416–421.
  86. O’Carroll, D., S. Erhardt, M. Pagani, S.C. Barton, M.A. Surani, T. Jenuwein (2001) The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol 21: 4330–4336.
  87. Ogawa, M., Y. Hiraoka, K. Taniguchi, S. Aiso (1998) Cloning and expression of a human/mouse Polycomb group gene, ENX-2/Enx-2. Biochim Biophys Acta 1395: 151–158.
  88. Ostroukhova, M., Z. Qi, T.B. Oriss, B. Dixon-McCarthy, P. Ray, A. Ray (2006) Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane- bound TGF-beta. J Clin Invest 116: 996– 1004.
  89. Pantazis, P., W.M. Bonner (1984) Specific alterations in the pattern of histone-3 synthesis during conversion of human leukemic cells to terminally differentiated cells in culture. Differentiation 28: 186–190.
  90. Pasini, D., A.P. Bracken, K. Helin (2004) Polycomb group proteins in cell cycle progression and cancer. Cell Cycle 3: 396–400.
  91. Pasini, D., A.P. Bracken, M.R. Jensen, E.L. Denchi, K. Helin (2004) Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J 23: 4061–4071.
  92. Plath, K., J. Fang, S.K. Mlynarczyk-Evans, R. Cao, K.A. Worringer, H. Wang, C.C. de la Cruz, A.P. Otte, B. Panning, Y. Zhang (2003) Role of histone H3 lysine 27 methylation in X inactivation. Science 300: 131–135.
  93. Postlethwaite, A.E., H. Shigemitsu, S. Kanangat (2004) Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol 16: 733–738.
  94. Quandt, K., K. Frech, H. Karas, E. Wingender, T. Werner (1995) MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res 23: 4878–4884.
  95. Raaphorst, F.M. (2005) Deregulated expression of Polycomb-group oncogenes in human malignant lymphomas and epithelial tumors. Hum Mol Genet 14(Spec No 1): R93–R100.
  96. Raaphorst, F.M., C.J. Meijer, E. Fieret, T. Blokzijl, E. Mommers, H. Buerger, J. Packeisen, R.A. Sewalt, A.P. Otte, P.J. van Diest (2003) Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene. Neoplasia 5: 481–488.
  97. Radtke, F., K. Raj (2003) The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer 3: 756–767.
  98. Ringrose, L., R. Paro (2004) Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu Rev Genet 38: 413–443.
  99. Roberts, A.B., L.M. Wakefield (2003) The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 100: 8621–8623.
  100. Sakata, Y., N. Koibuchi, F. Xiang, J.M. Youngblood, C.N. Kamei, M.T. Chin (2006) The spectrum of cardiovascular anomalies in CHF1/Hey2 deficient mice reveals roles in endocardial cushion, myocardial and vascular maturation. J Mol Cell Cardiol 40: 267–273.
  101. Saramaki, O.R., T.L. Tammela, P.M. Martikainen, R.L. Vessella, T. Visakorpi (2006) The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer. Genes Chromosomes Cancer 45: 639–645.
  102. Sasai, Y., R. Kageyama, Y. Tagawa, R. Shigemoto, S. Nakanishi (1992) Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev 6: 2620–2634.
  103. Sato, N., D. Takahashi, S.M. Chen, R. Tsuchiya, T. Mukoyama, S. Yamagata, M. Ogawa, M. Yoshida, S. Kondo, N. Satoh, S. Ueda (2004) Acute nephrotoxicity of aristolochic acids in mice. J Pharm Pharmacol 56: 221–229.
  104. Schwartz, B.E., K. Ahmad (2005) Transcriptional activation triggers deposition and removal of the histone variant H3.3. Genes Dev 19: 804–814.
  105. Shao, Z., F. Raible, R. Mollaaghababa, J.R. Guyon, C.T. Wu, W. Bender, R.E. Kingston (1999) Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98: 37–46.
  106. Shawber, C., D. Nofziger, J.J. Hsieh, C. Lindsell, O. Bogler, D. Hayward, G. Weinmaster (1996) Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway. Development 122: 3765–3773.
  107. Shi, Y., F. Lan, C. Matson, P. Mulligan, J.R. Whetstine, P.A. Cole, R.A. Casero, Y. Shi (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119: 941–953.
  108. Shook, D., R. Keller (2003) Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 120: 1351–1383.
  109. Silva, J., W. Mak, I. Zvetkova, R. Appanah, T.B. Nesterova, Z. Webster, A.H. Peters, T. Jenuwein, A.P. Otte, N. Brockdorff (2003) Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell 4: 481–495.
  110. Song, M.H., F.Z. Huang, F.C. Gonsalves, D.A. Weisblat (2004) Cell cycle-dependent expression of a hairy and Enhancer of split (hes) homolog during cleavage and segmentation in leech embryos. Dev Biol 269: 183–195.
  111. Stopka, T., D.F. Amanatullah, M. Papetti, A.I. Skoultchi (2005) PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure. EMBO J 24: 3712–3723.
  112. Strahl, B.D., C.D. Allis (2000) The language of covalent histone modifications. Nature 403: 41–45.
  113. Su, I.H., M.W. Dobenecker, E. Dickinson, M. Oser, A. Basavaraj, R. Marqueron, A. Viale, D. Reinberg, C. Wulfing, A. Tarakhovsky (2005) Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell 121: 425–436.
  114. Sun, J., C.N. Kamei, M.D. Layne, M.K. Jain, J.K. Liao, M.E. Lee, M.T. Chin (2001) Regulation of myogenic terminal differentiation by the hairy-related transcription factor CHF2. J Biol Chem 276: 18591–18596.
  115. Sun, Y., W. Lowther, K. Kato, C. Bianco, N. Kenney, L. Strizzi, D. Raafat, M. Hirota, N.I. Khan, S. Bargo, B. Jones, D. Salomon, R. Callahan (2005) Notch4 intracellular domain binding to Smad3 and inhibition of the TGF-beta signaling. Oncogene 24: 5365–5374.
  116. Takizawa, T., W. Ochiai, K. Nakashima, T. Taga (2003) Enhanced gene activation by Notch and BMP signaling cross-talk. Nucleic Acids Res 31: 5723–5731.
  117. Tang, X., M. Milyavsky, I. Shats, N. Erez, N. Goldfinger, V. Rotter (2004) Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene 23: 5759–5769.
  118. Thiery, J.P. (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2: 442–454.
  119. Thiery, J.P., J.P. Sleeman (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7: 131–142.
  120. Timmerman, L.A., J. Grego-Bessa, A. Raya, E. Bertran, J.M. Perez-Pomares, J. Diez, S. Aranda, S. Palomo, F. McCormick, J.C. Izpisua-Belmonte, J.L. de la Pompa (2004) Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18: 99–115.
  121. Tsukada, Y., J. Fang, H. Erdjument-Bromage, M.E. Warren, C.H. Borchers, P. Tempst, Y. Zhang (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439: 811–816.
  122. Umbhauer, M., J.C. Boucaut, D.L. Shi (2001) Repression of XMyoD expression and myogenesis by Xhairy-1 in Xenopus early embryo. Mech Dev 109: 61–68.
  123. Valk-Lingbeek, M.E., S.W. Bruggeman, M. van Lohuizen (2004) Stem cells and cancer; the polycomb connection. Cell 118: 409–418.
  124. van Lohuizen, M., M. Tijms, J.W. Voncken, A. Schumacher, T. Magnuson, E. Wientjens (1998) Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. Mol Cell Biol 18: 3572–3579.
  125. Varambally, S., S.M. Dhanasekaran, M. Zhou, T.R. Barrette, C. Kumar-Sinha, M.G. Sanda, D. Ghosh, K.J. Pienta, R.G. Sewalt, A.P. Otte, M.A. Rubin, A.M. Chinnaiyan (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419: 624–629.
  126. Vire, E., C. Brenner, R. Deplus, L. Blanchon, M. Fraga, C. Didelot, L. Morey, A. Van Eynde, D. Bernard, J.M. Vanderwinden, M. Bollen, M. Esteller, L. Di Croce, Y. de Launoit, F. Fuks (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439: 871–874.
  127. Visser, H.P., M.J. Gunster, H.C. Kluin-Nelemans, E.M. Manders, F.M. Raaphorst, C.J. Meijer, R. Willemze, A.P. Otte (2001) The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma. Br J Haematol 112: 950–958.
  128. Wang, Y., J. Wysocka, J. Sayegh, Y.H. Lee, J.R. Perlin, L. Leonelli, L.S. Sonbuchner, C.H. McDonald, R.G. Cook, Y. Dou, R.G. Roeder, S. Clarke, M.R. Stallcup, C.D. Allis, S.A. Coonrod (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306: 279–283.
  129. Weijzen, S., P. Rizzo, M. Braid, R. Vaishnav, S.M. Jonkheer, A. Zlobin, B.A. Osborne, S. Gottipati, J.C. Aster, W.C. Hahn, M. Rudolf, K. Siziopikou, W.M. Kast, L. Miele (2002) Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 8: 979–986.
  130. Wellman, S.E., P.J. Casano, D.R. Pilch, W.F. Marzluff, D.B. Sittman (1987) Characterization of mouse H3.3-like histone genes. Gene 59: 29–39.
  131. Weng, A.P., J.C. Aster (2004) Multiple niches for Notch in cancer: context is everything. Curr Opin Genet Dev 14: 48–54.
  132. Whetstine, J.R., A. Nottke, F. Lan, M. Huarte, S. Smolikov, Z. Chen, E. Spooner, E. Li, G. Zhang, M. Colaiacovo, Y. Shi (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125: 467–481.
  133. Wirbelauer, C., O. Bell, D. Schubeler (2005) Variant histone H3.3 is deposited at sites of nucleosomal displacement throughout transcribed genes while active histone modifications show a promoter-proximal bias. Genes Dev 19: 1761–1766.
  134. Wu, R.S., S. Tsai, W.M. Bonner (1982) Patterns of histone variant synthesis can distinguish G0 from G1 cells. Cell 31: 367–374.
  135. Wunsch, A.M., J. Lough (1987) Modulation of histone H3 variant synthesis during the myoblast-myotube transition of chicken myogenesis. Dev Biol 119: 94–99.
  136. Yamane, K., C. Toumazou, Y.I. Tsukada, H. Erdjument-Bromage, P. Tempst, J. Wong, Y. Zhang (2006) JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell 125: 483–495.
  137. Zavadil, J., M. Bitzer, D. Liang, Y.C. Yang, A. Massimi, S. Kneitz, E. Piek, E.P. Bottinger (2001) Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci USA 98: 6686–6691.
  138. Zavadil, J., E.P. Bottinger (2005) TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 24: 5764–5774.
  139. Zavadil, J., L. Cermak, N. Soto-Nieves, E.P. Bottinger (2004) Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J 23: 1155–1165.


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