Publikationsserver der Universitätsbibliothek Marburg

Funktion des ATP-abhängigen Chromatin Remodelers Mi-2 in der Regulation von Ecdyson-abhängigen Genen in Drosophila melanogaster
Titel:Function of the ATP-dependent chromatin remodeler Mi-2 in the regulation of ecdysone dependent genes in Drosophila melanogaster
Autor:Kreher, Judith
Weitere Beteiligte: Brehm, Alexander (Prof. Dr.)
URN: urn:nbn:de:hebis:04-z2014-06466
DDC: Biowissenschaften, Biologie


Drosophila, Chromatin, Nuclear receptor, Drosophila, Nucleosom, Chromatin, Kernrezeptor, Nucleosome

The development of the fruitfly Drosophila melanogaster is regulated by the steroid hormone ecdysone. Ecdysone is released at the onset of metamorphosis and initiates a cascade of transcriptional events. First, it leads to the heterodimerisation of the Ecdysone receptor (EcR) with its binding partner ultraspiracle. This complex recruits the transcription machinery to ecdysone inducible genes and thereby initiates transcription of genes that contribute to pupariation and metamorphosis. ATP-dependent chromatin remodelers regulate transcription by altering DNA accessibility and often reside in multimeric protein complexes. Mi-2 is a member of the CHD family of ATP-dependent chromatin remodelers and can function both as co-repressor and co-activator in transcription regulation. The results described in this thesis investigate the function of the chromatin remodeler Mi-2 in the regulation of ecdysone dependent genes. Further, they provide a model by which Mi-2 is targeted to and influences transcription of ecdysone dependent genes. In the first part of this thesis, genome-wide Mi-2 binding sites were mapped by chromatin immunoprecipitation followed by DNA-Sequencing (ChIPSeq) in untreated and ecdysone treated Drosophila S2 cells. This led to the identification of 103 Mi-2 binding sites that show increased binding of Mi-2 upon hormonal stimulation. Further analyses showed that a significant proportion of these binding sites resides in the close proximity of ecdysone inducible genes, implicating that Mi-2 functions in the regulation of these loci. Six ecdysone induced Mi-2 binding sites at two ecdysone dependent genes, the vrille and the broad loci were investigated in more detail. Here, depletion of Mi-2 resulted in a strong increase in expression of these genes in untreated and ecdysone treated cells. However, depletion of a different ATP-dependent chromatin remodeler, Iswi, did not result in derepression of broad and vrille, indicating that Mi-2 function is specific at the broad and vrille genes. In the second part of this thesis, interaction studies revealed that Mi-2 can bind to EcR. This interaction was found to be independent of the hormone ecdysone. Further, the interaction between Mi-2 and EcR was mapped to the ATPase domain of Mi-2. These results demonstrated the first described interaction between the catalytic domain of Mi-2 and a nuclear receptor. In addition, the activation function 2 (AF2 domain) of EcR was found to be important for the interaction with Mi-2. The finding that Mi-2 and EcR can physically interact led to the hypothesis that EcR can recruit Mi-2 to specific sites in the genome. Indeed, a significant overlap between EcR and Mi-2 binding sites was found in both untreated and ecdysone treated cells. In agreement with this hypothesis, depletion of EcR led to decreased ecdysone induced Mi-2 recruitment to the vrille and broad genes. These findings established a new recruitment model for Mi-2 by EcR to chromatin. Finally, Micrococcal nuclease (MNase) mapping demonstrated that Mi-2 functions at the vrille gene by maintaining a closed chromatin structure at this locus. Here, depletion of Mi-2 resulted in a more open chromatin structure, which correlated with an increase in expression of vrille.

Bibliographie / References

  1. Laemmli, U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-5 (1970).
  2. Murawska, M. Functional characterization of ATP-dependent chromatin remodelers of the CHD family of Drosophila, Philipps-University Marburg (2011).
  3. Meier, K. Identification and functional characterisation of dL(3)mbt-containing complexes in Drosophila melanogaster, Philipps-University Marburg (2012).
  4. Mathieu, E.-L. Genome-wide analysis of dMi-2 binding sites, Philipps-University Marburg (2013).
  5. Kharchenko, P.V. et al. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471, 480-5 (2011).
  6. Talbot, W.S., Swyryd, E.A. and Hogness, D.S. Drosophila tissues with different metamorphic responses to ecdysone express different ecdysone receptor isoforms. Cell 73, 1323-37 (1993).
  7. Lamond, A.I. and Earnshaw, W.C. Structure and function in the nucleus. Science 280, 547-53 (1998).
  8. Smagghe, G., Goodman, C.L. and Stanley, D. Insect cell culture and applications to research and pest management. In Vitro Cell Dev Biol Anim 45, 93-105 (2009).
  9. Jiang, C., Baehrecke, E.H. and Thummel, C.S. Steroid regulated programmed cell death during Drosophila metamorphosis. Development 124, 4673-83 (1997).
  10. Schubiger, M., Wade, A.A., Carney, G.E., Truman, J.W. and Bender, M. Drosophila EcR-B ecdysone receptor isoforms are required for larval molting and for neuron remodeling during metamorphosis. Development 125, 2053-62 (1998).
  11. Papoulas, O., Beek, S.J., Moseley, S.L., McCallum, C.M., Sarte, M., Shearn, A. and Tamkun, J.W. The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes. Development 125, 3955-66 (1998).
  12. Schneider, I. Cell lines derived from late embryonic stages of Drosophila melanogaster. J Embryol Exp Morphol 27, 353-65 (1972).
  13. Tatham, M.H., Rodriguez, M.S., Xirodimas, D.P. and Hay, R.T. Detection of protein SUMOylation in vivo. Nat Protoc 4, 1363-71 (2009).
  14. Ornaghi, P., Ballario, P., Lena, A.M., Gonzalez, A. and Filetici, P. The bromodomain of Gcn5p interacts in vitro with specific residues in the N terminus of histone H4. J Mol Biol 287, 1-7 (1999).
  15. Smagghe, G. Ecdysone, structures and functions. xlii, 583 p. (2009).
  16. Tsukiyama, T., Daniel, C., Tamkun, J. and Wu, C. ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor. Cell 83, 1021-6 (1995).
  17. Sawatsubashi, S. et al. Ecdysone receptor-dependent gene regulation mediates histone poly(ADP-ribosyl)ation. Biochem Biophys Res Commun 320, 268-72 (2004).
  18. Seliga, J., Bielska, K., Wieczorek, E., Orlowski, M., Niedenthal, R. and Ozyhar, A. Multidomain sumoylation of the ecdysone receptor (EcR) from Drosophila melanogaster. J Steroid Biochem Mol Biol 138, 162-73 (2013).
  19. Ruthenburg, A.J., Allis, C.D. and Wysocka, J. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell 25, 15-30 (2007).
  20. Yin, V.P. and Thummel, C.S. Mechanisms of steroid-triggered programmed cell death in Drosophila. Semin Cell Dev Biol 16, 237-43 (2005).
  21. Maurer-Stroh, S., Dickens, N.J., Hughes-Davies, L., Kouzarides, T., Eisenhaber, F. and Ponting, C.P. The Tudor domain 'Royal Family': Tudor, plant Agenet, Chromo, PWWP and MBT domains. Trends Biochem Sci 28, 69-74 (2003).
  22. Lo, W.S., Trievel, R.C., Rojas, J.R., Duggan, L., Hsu, J.Y., Allis, C.D., Marmorstein, R. and Berger, S.L. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol Cell 5, 917-26 (2000).
  23. Li, T.R. and White, K.P. Tissue-specific gene expression and ecdysone-regulated genomic networks in Drosophila. Dev Cell 5, 59-72 (2003).
  24. Polo, S.E., Kaidi, A., Baskcomb, L., Galanty, Y. and Jackson, S.P. Regulation of DNA- damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. EMBO J 29, 3130-9 (2010).
  25. Wysocka, J. et al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442, 86-90 (2006).
  26. Schneider, R., Bannister, A.J., Myers, F.A., Thorne, A.W., Crane-Robinson, C. and Kouzarides, T. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 6, 73-7 (2004).
  27. Luger, K., Dechassa, M.L. and Tremethick, D.J. New insights into nucleosome and chromatin structure: an ordered state or a disordered affair? Nat Rev Mol Cell Biol 13, 436-47 (2012).
  28. Malik, H.S. and Henikoff, S. Phylogenomics of the nucleosome. Nat Struct Biol 10, 882-91 (2003).
  29. Zentner, G.E. and Henikoff, S. Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20, 259-66 (2013).
  30. Wu, W.H., Alami, S., Luk, E., Wu, C.H., Sen, S., Mizuguchi, G., Wei, D. and Wu, C. Swc2 is a widely conserved H2AZ-binding module essential for ATP-dependent histone exchange. Nat Struct Mol Biol 12, 1064-71 (2005).
  31. Lusser, A., Urwin, D.L. and Kadonaga, J.T. Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly. Nat Struct Mol Biol 12, 160-6 (2005).
  32. Mu, J.J., Wang, Y., Luo, H., Leng, M., Zhang, J., Yang, T., Besusso, D., Jung, S.Y. and Qin, J. A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM- Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints. J Biol Chem 282, 17330-4 (2007).
  33. Wu, L. and Winston, F. Evidence that Snf-Swi controls chromatin structure over both the TATA and UAS regions of the SUC2 promoter in Saccharomyces cerevisiae. Nucleic Acids Res 25, 4230-4 (1997).
  34. Jakob, M. et al. Novel DNA-binding element within the C-terminal extension of the nuclear receptor DNA-binding domain. Nucleic Acids Res 35, 2705-18 (2007).
  35. Morettini, S. et al. The chromodomains of CHD1 are critical for enzymatic activity but less important for chromatin localization. Nucleic Acids Res 39, 3103-15 (2011).
  36. Mathieu, E.L., Finkernagel, F., Murawska, M., Scharfe, M., Jarek, M. and Brehm, A. Recruitment of the ATP-dependent chromatin remodeler dMi-2 to the transcribed region of active heat shock genes. Nucleic Acids Res 40, 4879-91 (2012).
  37. Rosenfeld, C.S. Animal models to study environmental epigenetics. Biol Reprod 82, 473-88 (2010).
  38. Tulin, A., Stewart, D. and Spradling, A.C. The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development. Genes Dev 16, 2108-19 (2002).
  39. McInerney, E.M. et al. Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation. Genes Dev 12, 3357-68 (1998).
  40. Zhang, Y., Ng, H.H., Erdjument-Bromage, H., Tempst, P., Bird, A. and Reinberg, D. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13, 1924-35 (1999).
  41. Ramirez-Carrozzi, V.R., Nazarian, A.A., Li, C.C., Gore, S.L., Sridharan, R., Imbalzano, A.N. and Smale, S.T. Selective and antagonistic functions of SWI/SNF and Mi- 2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev 20, 282-96 (2006).
  42. Sawatsubashi, S. et al. A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor. Genes Dev 24, 159-70 (2010).
  43. Klymenko, T., Papp, B., Fischle, W., Kocher, T., Schelder, M., Fritsch, C., Wild, B., Wilm, M. and Muller, J. A Polycomb group protein complex with sequence- specific DNA-binding and selective methyl-lysine-binding activities. Genes Dev 20, 1110-22 (2006).
  44. Segraves, W.A. and Hogness, D.S. The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid receptor superfamily. Genes Dev 4, 204-19 (1990).
  45. Matsuoka, S. et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-6 (2007).
  46. Jacobs, S.A. and Khorasanizadeh, S. Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295, 2080-3 (2002).
  47. Kozlova, T. and Thummel, C.S. Essential roles for ecdysone signaling during Drosophila mid-embryonic development. Science 301, 1911-4 (2003).
  48. Ruiz-Carrillo, A., Wangh, L.J. and Allfrey, V.G. Processing of newly synthesized histone molecules. Science 190, 117-28 (1975).
  49. Samuels, H.H., Tsai, J.S. and Cintron, R. Thyroid hormone action: a cell-culture system responsive to physiological concentrations of thyroid hormones. Science 181, 1253-6 (1973).
  50. Mohrmann, L., Langenberg, K., Krijgsveld, J., Kal, A.J., Heck, A.J. and Verrijzer, C.P. Differential targeting of two distinct SWI/SNF-related Drosophila chromatin- remodeling complexes. Mol Cell Biol 24, 3077-88 (2004).
  51. Vorobyeva, N.E., Nikolenko, J.V., Krasnov, A.N., Kuzmina, J.L., Panov, V.V., Nabirochkina, E.N., Georgieva, S.G. and Shidlovskii, Y.V. SAYP interacts with DHR3 nuclear receptor and participates in ecdysone-dependent transcription regulation. Cell Cycle 10, 1821-7 (2011).
  52. Morgan, T.H. The mechanism of Mendelian heredity, xiii, 262 p. (Holt, New York) (1915).
  53. Murawska, M., Hassler, M., Renkawitz-Pohl, R., Ladurner, A. and Brehm, A. Stress- induced PARP activation mediates recruitment of Drosophila Mi-2 to promote heat shock gene expression. PLoS Genet 7, e1002206 (2011).
  54. Metivier, R. et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature 452, 45-50 (2008).
  55. Robins, D.M., Paek, I., Seeburg, P.H. and Axel, R. Regulated expression of human growth hormone genes in mouse cells. Cell 29, 623-31 (1982).
  56. Mendel, G.J. and Tschermak, E. Versuche über Pflanzenhybriden zwei Abhandlungen (1865 und 1869), 62 S. (Engelmann, Leipzig) (1901).
  57. Kilpatrick, Z.E., Cakouros, D. and Kumar, S. Ecdysone-mediated up-regulation of the effector caspase DRICE is required for hormone-dependent apoptosis in Drosophila cells. J Biol Chem 280, 11981-6 (2005).
  58. Van Hooser, A.A. et al. Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci 114, 3529-42 (2001).
  59. Woodard, C.T., Baehrecke, E.H. and Thummel, C.S. A molecular mechanism for the stage specificity of the Drosophila prepupal genetic response to ecdysone. Cell 79, 607-15 (1994).
  60. Wade, P.A., Jones, P.L., Vermaak, D. and Wolffe, A.P. A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Curr Biol 8, 843-6 (1998).
  61. Sakabe, K., Wang, Z. and Hart, G.W. Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc Natl Acad Sci U S A 107, 19915-20 (2010).
  62. Tulin, A. and Spradling, A. Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science 299, 560-2 (2003).
  63. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693-705 (2007).
  64. Shang, Y., Hu, X., DiRenzo, J., Lazar, M.A. and Brown, M. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103, 843-52 (2000).
  65. Meneghini, M.D., Wu, M. and Madhani, H.D. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112, 725- 36 (2003).
  66. Reid, G., Hubner, M.R., Metivier, R., Brand, H., Denger, S., Manu, D., Beaudouin, J., Ellenberg, J. and Gannon, F. Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell 11, 695-707 (2003).
  67. Rewitz, K.F., Yamanaka, N. and O'Connor, M.B. Developmental checkpoints and feedback circuits time insect maturation. Curr Top Dev Biol 103, 1-33 (2013).
  68. Lyko, F., Ramsahoye, B.H. and Jaenisch, R. DNA methylation in Drosophila melanogaster. Nature 408, 538-40 (2000).
  69. Scully, R. and Xie, A. Double strand break repair functions of histone H2AX. Mutat Res 750, 5-14 (2013).
  70. Yao, T.P., Segraves, W.A., Oro, A.E., McKeown, M. and Evans, R.M. Drosophila ultraspiracle modulates ecdysone receptor function via heterodimer formation. Cell 71, 63-72 (1992).
  71. Yamanaka, N., Rewitz, K.F. and O'Connor, M.B. Ecdysone control of developmental transitions: lessons from Drosophila research. Annu Rev Entomol 58, 497-516 (2013).
  72. Saiki, R.K., Scharf, S., Faloona, F., Mullis, K.B., Horn, G.T., Erlich, H.A. and Arnheim, N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230, 1350-4 (1985).
  73. Metivier, R., Penot, G., Hubner, M.R., Reid, G., Brand, H., Kos, M. and Gannon, F. Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115, 751-63 (2003).
  74. Thummel, C.S. From embryogenesis to metamorphosis: the regulation and function of Drosophila nuclear receptor superfamily members. Cell 83, 871-7 (1995).
  75. Yao, T.P., Forman, B.M., Jiang, Z., Cherbas, L., Chen, J.D., McKeown, M., Cherbas, P. and Evans, R.M. Functional ecdysone receptor is the product of EcR and Ultraspiracle genes. Nature 366, 476-9 (1993).
  76. Shahbazian, M.D. and Grunstein, M. Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76, 75-100 (2007).
  77. Neigeborn, L. and Carlson, M. Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics 108, 845-58 (1984).
  78. Vogtli, M., Elke, C., Imhof, M.O. and Lezzi, M. High level transactivation by the ecdysone receptor complex at the core recognition motif. Nucleic Acids Res 26, 2407-14 (1998).
  79. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P. and Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature 439, 811-6 (2006).
  80. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A., Casero, R.A. and Shi, Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119, 941-53 (2004).
  81. Skene, P.J. and Henikoff, S. Histone variants in pluripotency and disease. Development 140, 2513-24 (2013).
  82. Nettles, K.W. and Greene, G.L. Ligand control of coregulator recruitment to nuclear receptors. Annu Rev Physiol 67, 309-33 (2005).
  83. Levine, M., Cattoglio, C. and Tjian, R. Looping back to leap forward: transcription enters a new era. Cell 157, 13-25 (2014).
  84. Stunnenberg, H.G. Mechanisms of transactivation by retinoic acid receptors. Bioessays 15, 309-15 (1993).
  85. White, K.P., Rifkin, S.A., Hurban, P. and Hogness, D.S. Microarray analysis of Drosophila development during metamorphosis. Science 286, 2179-84 (1999).
  86. Wright, L.G., Chen, T., Thummel, C.S. and Guild, G.M. Molecular characterization of the 71E late puff in Drosophila melanogaster reveals a family of novel genes. J Mol Biol 255, 387-400 (1996).
  87. Sambrook, J. and Russell, D.W. Molecular cloning a laboratory manual, 3 vols. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York) (2001).
  88. Jang, K.S., Paik, S.S., Chung, H., Oh, Y.H. and Kong, G. MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers. Cancer Sci 97, 374-9 (2006).
  89. Soshnikova, N.V., Vorob'eva, N.E., Krasnov, A.N., Georgieva, S.G., Nabirochkina, E.N. and Shidlovskii Iu, V. [Novel complex, formed by transcription coactivator SAYP]. Mol Biol (Mosk) 43, 1055-62 (2009).
  90. Olefsky, J.M. Nuclear receptor minireview series. J Biol Chem 276, 36863-4 (2001).
  91. Nagy, L., Kao, H.Y., Chakravarti, D., Lin, R.J., Hassig, C.A., Ayer, D.E., Schreiber, S.L. and Evans, R.M. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell 89, 373-80 (1997).
  92. NURD-associated protein p66 in Drosophila. Genetics 169, 2087-100 (2005).
  93. Morris, S.A., Baek, S., Sung, M.H., John, S., Wiench, M., Johnson, T.A., Schiltz, R.L. and Hager, G.L. Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions. Nat Struct Mol Biol 21, 73-81 (2014).
  94. Peters, A.H. et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 12, 1577-89 (2003).
  95. Tsukiyama, T. and Wu, C. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell 83, 1011-20 (1995).
  96. Oro, A.E., McKeown, M. and Evans, R.M. Relationship between the product of the Drosophila ultraspiracle locus and the vertebrate retinoid X receptor. Nature 347, 298-301 (1990).
  97. Mujtaba, S. et al. Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell 13, 251-63 (2004).
  98. Trievel, R.C., Beach, B.M., Dirk, L.M., Houtz, R.L. and Hurley, J.H. Structure and catalytic mechanism of a SET domain protein methyltransferase. Cell 111, 91- 103 (2002).
  99. Kopeć, S. Studies on the Necessity of the Brain for the Inception of Insect Metamorphosis. Biological Bulletin 42, 323-342 (1922).
  100. Ng, H.H., Robert, F., Young, R.A. and Struhl, K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 11, 709-19 (2003).
  101. Zhang, Y., LeRoy, G., Seelig, H.P., Lane, W.S. and Reinberg, D. The dermatomyositis- specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95, 279-89 (1998).
  102. Koelle, M.R., Talbot, W.S., Segraves, W.A., Bender, M.T., Cherbas, P. and Hogness, D.S. The Drosophila EcR gene encodes an ecdysone receptor, a new member of the steroid receptor superfamily. Cell 67, 59-77 (1991).
  103. Vaughn, J.L., Goodwin, R.H., Tompkins, G.J. and McCawley, P. The establishment of two cell lines from the insect Spodoptera frugiperda (Lepidoptera; Noctuidae).
  104. Richards, G. The radioimmune assay of ecdysteroid titres in Drosophila melanogaster. Mol Cell Endocrinol 21, 181-97 (1981).
  105. Mazumdar, A., Wang, R.A., Mishra, S.K., Adam, L., Bagheri-Yarmand, R., Mandal, M., Vadlamudi, R.K. and Kumar, R. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3, 30-7 (2001).
  106. Le Guezennec, X., Vermeulen, M., Brinkman, A.B., Hoeijmakers, W.A., Cohen, A., Lasonder, E. and Stunnenberg, H.G. MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol 26, 843-51 (2006).
  107. Varga-Weisz, P.D., Wilm, M., Bonte, E., Dumas, K., Mann, M. and Becker, P.B. Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature 388, 598-602 (1997).
  108. Mangelsdorf, D.J. et al. The nuclear receptor superfamily: the second decade. Cell 83, 835-9 (1995).
  109. Seelig, H.P., Moosbrugger, I., Ehrfeld, H., Fink, T., Renz, M. and Genth, E. The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum 38, 1389-99 (1995).
  110. Mendiburo, M.J., Padeken, J., Fulop, S., Schepers, A. and Heun, P. Drosophila CENH3 is sufficient for centromere formation. Science 334, 686-90 (2011).
  111. Nuclear Receptors Nomenclature, C. A unified nomenclature system for the nuclear receptor superfamily. Cell 97, 161-3 (1999).
  112. Mendoza-Parra, M.A. and Gronemeyer, H. Genome-wide studies of nuclear receptors in cell fate decisions. Semin Cell Dev Biol 24, 706-15 (2013).
  113. Manelyte, L. and Längst, G. Chromatin Remodelers and Their Way of Action. in Chromatin Remodeling (ed. Radzioch, D.) (InTech, 2013).
  114. Sewack, G.F. and Hansen, U. Nucleosome positioning and transcription-associated chromatin alterations on the human estrogen-responsive pS2 promoter. J Biol Chem 272, 31118-29 (1997).
  115. Thomas, H.E., Stunnenberg, H.G. and Stewart, A.F. Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle. Nature 362, 471-5 (1993).
  116. Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F. and Richmond, T.J. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251- 60 (1997).
  117. Tong, J.K., Hassig, C.A., Schnitzler, G.R., Kingston, R.E. and Schreiber, S.L. Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature 395, 917-21 (1998).
  118. Santos-Rosa, H., Schneider, R., Bannister, A.J., Sherriff, J., Bernstein, B.E., Emre, N.C., Schreiber, S.L., Mellor, J. and Kouzarides, T. Active genes are tri- methylated at K4 of histone H3. Nature 419, 407-11 (2002).
  119. Maletta, M., Orlov, I., Roblin, P., Beck, Y., Moras, D., Billas, I.M. and Klaholz, B.P. The palindromic DNA-bound USP/EcR nuclear receptor adopts an asymmetric organization with allosteric domain positioning. Nat Commun 5, 4139 (2014).
  120. Osborne, C.S. et al. Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36, 1065-71 (2004).
  121. Pepke, S., Wold, B. and Mortazavi, A. Computation for ChIP-seq and RNA-seq studies. Nat Methods 6, S22-32 (2009).
  122. Kodani, M. The Protein of the Salivary Gland Secretion in Drosophila. Proc Natl Acad Sci U S A 34, 131-5 (1948).
  123. Murawsky, C.M., Brehm, A., Badenhorst, P., Lowe, N., Becker, P.B. and Travers, A.A. Tramtrack69 interacts with the dMi-2 subunit of the Drosophila NuRD chromatin remodelling complex. EMBO Rep 2, 1089-94 (2001).
  124. Kiss, I., Beaton, A.H., Tardiff, J., Fristrom, D. and Fristrom, J.W. Interactions and developmental effects of mutations in the Broad-Complex of Drosophila melanogaster. Genetics 118, 247-59 (1988).
  125. Sliter, T.J. and Gilbert, L.I. Developmental arrest and ecdysteroid deficiency resulting from mutations at the dre4 locus of Drosophila. Genetics 130, 555-68 (1992).
  126. Raisner, R.M., Hartley, P.D., Meneghini, M.D., Bao, M.Z., Liu, C.L., Schreiber, S.L., Rando, O.J. and Madhani, H.D. Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin. Cell 123, 233-48 (2005).
  127. Marygold, S.J. et al. The ribosomal protein genes and Minute loci of Drosophila melanogaster. Genome Biol 8, R216 (2007).
  128. Murawska, M., Kunert, N., van Vugt, J., Langst, G., Kremmer, E., Logie, C. and Brehm, A. dCHD3, a novel ATP-dependent chromatin remodeler associated with sites of active transcription. Mol Cell Biol 28, 2745-57 (2008).
  129. Petesch, S.J. and Lis, J.T. Rapid, transcription-independent loss of nucleosomes over a large chromatin domain at Hsp70 loci. Cell 134, 74-84 (2008).
  130. Srinivasan, S., Dorighi, K.M. and Tamkun, J.W. Drosophila Kismet regulates histone H3 lysine 27 methylation and early elongation by RNA polymerase II. PLoS Genet 4, e1000217 (2008).
  131. Kunert, N., Wagner, E., Murawska, M., Klinker, H., Kremmer, E. and Brehm, A. dMec: a novel Mi-2 chromatin remodelling complex involved in transcriptional repression. EMBO J 28, 533-44 (2009).
  132. Jang, A.C., Chang, Y.C., Bai, J. and Montell, D. Border-cell migration requires integration of spatial and temporal signals by the BTB protein Abrupt. Nat Cell Biol 11, 569-79 (2009).
  133. Kwon, S.Y., Xiao, H., Wu, C. and Badenhorst, P. Alternative splicing of NURF301 generates distinct NURF chromatin remodeling complexes with altered modified histone binding specificities. PLoS Genet 5, e1000574 (2009).
  134. Sedkov, Y. et al. Methylation at lysine 4 of histone H3 in ecdysone-dependent development of Drosophila. Nature 426, 78-83 (2003).
  135. Zhang, H., Roberts, D.N. and Cairns, B.R. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123, 219-31 (2005).
  136. Petryk, A. et al. Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone. Proc Natl Acad Sci U S A 100, 13773-8 (2003).
  137. Zhang, K., Chen, Y., Zhang, Z. and Zhao, Y. Identification and verification of lysine propionylation and butyrylation in yeast core histones using PTMap software. J Proteome Res 8, 900-6 (2009).
  138. Smeenk, G., Wiegant, W.W., Vrolijk, H., Solari, A.P., Pastink, A. and van Attikum, H. The NuRD chromatin-remodeling complex regulates signaling and repair of DNA damage. J Cell Biol 190, 741-9 (2010).
  139. Reddy, B.A., Bajpe, P.K., Bassett, A., Moshkin, Y.M., Kozhevnikova, E., Bezstarosti, K., Demmers, J.A., Travers, A.A. and Verrijzer, C.P. Drosophila transcription factor Tramtrack69 binds MEP1 to recruit the chromatin remodeler NuRD. Mol Cell Biol 30, 5234-44 (2010).
  140. Konev, A.Y. et al. CHD1 motor protein is required for deposition of histone variant H3.3 into chromatin in vivo. Science 317, 1087-90 (2007).
  141. Mansfield, R.E., Musselman, C.A., Kwan, A.H., Oliver, S.S., Garske, A.L., Davrazou, F., Denu, J.M., Kutateladze, T.G. and Mackay, J.P. Plant homeodomain (PHD) fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9. J Biol Chem 286, 11779-91 (2011).
  142. Li, G. and Reinberg, D. Chromatin higher-order structures and gene regulation. Curr Opin Genet Dev 21, 175-86 (2011).
  143. Szerlong, H.J. and Hansen, J.C. Nucleosome distribution and linker DNA: connecting nuclear function to dynamic chromatin structure. Biochem Cell Biol 89, 24-34 (2011).
  144. Sanchez, R. and Zhou, M.M. The PHD finger: a versatile epigenome reader. Trends Biochem Sci 36, 364-72 (2011).
  145. Ong, C.T. and Corces, V.G. Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet 12, 283-93 (2011).
  146. Wood, A.M., Van Bortle, K., Ramos, E., Takenaka, N., Rohrbaugh, M., Jones, B.C., Jones, K.C. and Corces, V.G. Regulation of chromatin organization and inducible gene expression by a Drosophila insulator. Mol Cell 44, 29-38 (2011).
  147. Johnston, D.M., Sedkov, Y., Petruk, S., Riley, K.M., Fujioka, M., Jaynes, J.B. and Mazo, A. Ecdysone-and NO-mediated gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development. Mol Cell 44, 51-61 (2011).
  148. Moshkin, Y.M. et al. Remodelers organize cellular chromatin by counteracting intrinsic histone-DNA sequence preferences in a class-specific manner. Mol Cell Biol 32, 675-88 (2012).
  149. Verdaasdonk, J.S. and Bloom, K. Centromeres: unique chromatin structures that drive chromosome segregation. Nat Rev Mol Cell Biol 12, 320-32 (2011).
  150. Nishino, Y. et al. Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure. EMBO J 31, 1644-53 (2012).
  151. Meier, K., Mathieu, E.L., Finkernagel, F., Reuter, L.M., Scharfe, M., Doehlemann, G., Jarek, M. and Brehm, A. LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes. PLoS Genet 8, e1002676 (2012).
  152. Luijsterburg, M.S. et al. A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure. EMBO J 31, 2511-27 (2012).
  153. Rossetto, D., Avvakumov, N. and Cote, J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics 7, 1098-108 (2012).
  154. O'Shaughnessy, A. and Hendrich, B. CHD4 in the DNA-damage response and cell cycle progression: not so NuRDy now. Biochem Soc Trans 41, 777-82 (2013).
  155. Tolstorukov, M.Y., Goldman, J.A., Gilbert, C., Ogryzko, V., Kingston, R.E. and Park, P.J. Histone variant H2A.Bbd is associated with active transcription and mRNA processing in human cells. Mol Cell 47, 596-607 (2012).
  156. Narlikar, G.J., Sundaramoorthy, R. and Owen-Hughes, T. Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes. Cell 154, 490-503 (2013).
  157. Rinn, J.L. and Chang, H.Y. Genome regulation by long noncoding RNAs. Annu Rev Biochem 81, 145-66 (2012).
  158. Stokes, D.G., Tartof, K.D. and Perry, R.P. CHD1 is concentrated in interbands and puffed regions of Drosophila polytene chromosomes. Proc Natl Acad Sci U S A 93, 7137-42 (1996).
  159. Wang, Q., Li, W., Liu, X.S., Carroll, J.S., Janne, O.A., Keeton, E.K., Chinnaiyan, A.M., Pienta, K.J. and Brown, M. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell 27, 380-92 (2007).
  160. Sobel, R.E., Cook, R.G., Perry, C.A., Annunziato, A.T. and Allis, C.D. Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4. Proc Natl Acad Sci U S A 92, 1237-41 (1995).
  161. Lavorgna, G., Karim, F.D., Thummel, C.S. and Wu, C. Potential role for a FTZ-F1 steroid receptor superfamily member in the control of Drosophila metamorphosis. Proc Natl Acad Sci U S A 90, 3004-8 (1993).
  162. Riddihough, G. and Pelham, H.R. An ecdysone response element in the Drosophila hsp27 promoter. EMBO J 6, 3729-34 (1987).
  163. Karim, F.D. and Thummel, C.S. Temporal coordination of regulatory gene expression by the steroid hormone ecdysone. EMBO J 11, 4083-93 (1992).
  164. Roder, K., Hung, M.S., Lee, T.L., Lin, T.Y., Xiao, H., Isobe, K.I., Juang, J.L. and Shen, C.J. Transcriptional repression by Drosophila methyl-CpG-binding proteins. Mol Cell Biol 20, 7401-9 (2000).
  165. Richards, G. Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster. IV. The mid prepupal period. Dev Biol 54, 256-63 (1976).
  166. Tamkun, J.W., Deuring, R., Scott, M.P., Kissinger, M., Pattatucci, A.M., Kaufman, T.C. and Kennison, J.A. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell 68, 561-72 (1992).
  167. Kimura, S. et al. Drosophila arginine methyltransferase 1 (DART1) is an ecdysone receptor co-repressor. Biochem Biophys Res Commun 371, 889-93 (2008).
  168. Kwon, S.Y., Xiao, H., Glover, B.P., Tjian, R., Wu, C. and Badenhorst, P. The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity. Dev Biol 316, 538-47 (2008).
  169. Radman-Livaja, M. and Rando, O.J. Nucleosome positioning: how is it established, and why does it matter? Dev Biol 339, 258-66 (2010).
  170. Truman, J.W. Hormonal control of insect ecdysis: endocrine cascades for coordinating behavior with physiology. Vitam Horm 73, 1-30 (2005).
  171. Langst, G., Bonte, E.J., Corona, D.F. and Becker, P.B. Nucleosome movement by CHRAC and ISWI without disruption or trans-displacement of the histone octamer. Cell 97, 843-52 (1999).
  172. Pokholok, D.K. et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517-27 (2005).
  173. Pauli, A., van Bemmel, J.G., Oliveira, R.A., Itoh, T., Shirahige, K., van Steensel, B. and Nasmyth, K. A direct role for cohesin in gene regulation and ecdysone response in Drosophila salivary glands. Curr Biol 20, 1787-98 (2010).
  174. Xue, Y., Wong, J., Moreno, G.T., Young, M.K., Cote, J. and Wang, W. NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell 2, 851-61 (1998).
  175. Tsai, C.C., Kao, H.Y., Yao, T.P., McKeown, M. and Evans, R.M. SMRTER, a Drosophila nuclear receptor coregulator, reveals that EcR-mediated repression is critical for development. Mol Cell 4, 175-86 (1999).
  176. Krogan, N.J. et al. The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Mol Cell 11, 721-9 (2003).
  177. Stielow, B., Sapetschnig, A., Kruger, I., Kunert, N., Brehm, A., Boutros, M. and Suske, G. Identification of SUMO-dependent chromatin-associated transcriptional repression components by a genome-wide RNAi screen. Mol Cell 29, 742-54 (2008).
  178. Shlyueva, D., Stelzer, C., Gerlach, D., Yanez-Cuna, J.O., Rath, M., Boryn, L.M., Arnold, C.D. and Stark, A. Hormone-responsive enhancer-activity maps reveal predictive motifs, indirect repression, and targeting of closed chromatin. Mol Cell 54, 180-92 (2014).
  179. Kehle, J., Beuchle, D., Treuheit, S., Christen, B., Kennison, J.A., Bienz, M. and Muller, J. dMi-2, a hunchback-interacting protein that functions in polycomb repression. Science 282, 1897-900 (1998).
  180. Kusch, T., Florens, L., Macdonald, W.H., Swanson, S.K., Glaser, R.L., Yates, J.R., 3rd, Abmayr, S.M., Washburn, M.P. and Workman, J.L. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science 306, 2084-7 (2004).
  181. Kobor, M.S., Venkatasubrahmanyam, S., Meneghini, M.D., Gin, J.W., Jennings, J.L., Link, A.J., Madhani, H.D. and Rine, J. A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol 2, E131 (2004).
  182. Marhold, J., Brehm, A. and Kramer, K. The Drosophila methyl-DNA binding protein MBD2/3 interacts with the NuRD complex via p55 and MI-2. BMC Mol Biol 5, 20 (2004).
  183. Kangaspeska, S., Stride, B., Metivier, R., Polycarpou-Schwarz, M., Ibberson, D., Carmouche, R.P., Benes, V., Gannon, F. and Reid, G. Transient cyclical methylation of promoter DNA. Nature 452, 112-5 (2008).
  184. King-Jones, K., Charles, J.P., Lam, G. and Thummel, C.S. The ecdysone-induced DHR4 orphan nuclear receptor coordinates growth and maturation in Drosophila. Cell 121, 773-84 (2005).
  185. Mosallanejad, H., Soin, T. and Smagghe, G. Selection for resistance to methoxyfenozide and 20-hydroxyecdysone in cells of the beet armyworm, Spodoptera exigua. Arch Insect Biochem Physiol 67, 36-49 (2008).
  186. Teytelman, L., Thurtle, D.M., Rine, J. and van Oudenaarden, A. Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins. Proc Natl Acad Sci U S A 110, 18602-7 (2013).

* Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten