Dokument

Summary:
The development of any multicellular organism involves the coordinated expression of different genes in complex spatio-temporal patterns. These complex patterns of gene expression result from the interplay between multiple transcription factors (TFs) and their co-factors, acting on specific cis-regulatory modules to activate or repress the affected locus. This study investigates the interaction between two essential regulators of myogenesis: the transcription factors Myocyte enhancing factor 2 (Mef2) and lame duck (lmd). Mutations in either of these transcription factors results in a similar block of fusion phenotype, but the molecular basis for this similar phenotype is not yet understood. The analysis started with ChIP-on-chip to identify the genomic location where each TF binds in vivo. Microarrays were used again to conduct expression profiling of loss-of-function mutants, and the combination of these two approaches yielded a list of direct target genes of the two TFs. Interestingly, the majority of enhancers bound by Lmd are also bound by Mef2 at the same developmental timepoint. Likewise, almost 80% of the lmd direct target genes are also direct targets of Mef2, revealing an extensive co-regulation between the two TFs. A group of shared direct targets was then selected for further study; Lmd and Mef2, alone or in combination, were used to drive ectopic expression of these genes, resulting in both synergistic and antagonistic interactions. The affected enhancer for each target was identified using a variety of predictions, and transgenic fly lines were created to demonstrate the capacity of the enhancers for correct expression in vivo. These enhancers were also analyzed in the mutant background of loss-of-function mutations and revealed specific requirements for each transcription factor. Lmd and Mef2 were also tested in vitro for their effect on transcription from these enhancers, revealing additive, cooperative, and repressive interactions. These results indicate that lmd is a temporal and tissue-specific modulator of Mef2 activity, acting both as a transcriptional activator and repressor on a sub- set of the catalog of target genes of Mef2. More generally, it demonstrates a scenario of flexibility in the regulatory output of two transcription factors, leading to additive, cooperative and repressive interactions.

Bibliographie / References

1. Stronach, B. E., Renfranz, P. J., Lilly, B., and Beckerle, M. C. (1999). Muscle LIM proteins are associated with muscle sarcomeres and require dMEF2 for their expression during Drosophila myogenesis. Mol Biol Cell 10, 2329-42.
2. Adams, M. D., et al. (2000). The genome sequence of Drosophila melanogaster. Science 287, 2185-95.
3. Halfon, M. S., Carmena, A., Gisselbrecht, S., Sackerson, C. M., Jimenez, F., Baylies, M. K., and Michelson, A. M. (2000). Ras pathway specificity is determined by the integration of multiple signal-activated and tissue- restricted transcription factors. Cell 103, 63-74.
4. Hinz, U., Wolk, A., and Renkawitz-Pohl, R. (1992). Ultrabithorax is a regulator of beta 3 tubulin expression in the Drosophila visceral mesoderm. Development 116, 543-54.
5. Brand, A. H., and Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401-15.
6. Callahan, C. A., Bonkovsky, J. L., Scully, A. L., and Thomas, J. B. (1996). derailed is required for muscle attachment site selection in Drosophila. Development 122, 2761-7.
7. Arnone, M. I., and Davidson, E. H. (1997). The hardwiring of development: organization and function of genomic regulatory systems. Development 124, 1851-64.
8. Ruiz-Gomez, M., Romani, S., Hartmann, C., Jackle, H., and Bate, M. (1997). Specific muscle identities are regulated by Kruppel during Drosophila embryogenesis. Development 124, 3407-14.
9. Yin, Z., Xu, X. L., and Frasch, M. (1997). Regulation of the twist target gene tinman by modular cis-regulatory elements during early mesoderm development. Development 124, 4971-82.
10. Price, M. A., and Kalderon, D. (1999). Proteolysis of cubitus interruptus in Drosophila requires phosphorylation by protein kinase A. Development 126, 4331-9.
11. Martin, B. S., Ruiz-Gomez, M., Landgraf, M., and Bate, M. (2001). A distinct set of founders and fusion-competent myoblasts make visceral muscles in the Drosophila embryo. Development 128, 3331-8.
12. Artero, R. D., Castanon, I., and Baylies, M. K. (2001). The immunoglobulin-like protein Hibris functions as a dose-dependent regulator of myoblast fusion and is differentially controlled by Ras and Notch signaling. Development 128, 4251-64.
13. Dworak, H. A., Charles, M. A., Pellerano, L. B., and Sink, H. (2001). Characterization of Drosophila hibris, a gene related to human nephrin. Development 128, 4265-76.
14. Onel, S. F., and Renkawitz-Pohl, R. (2009). FuRMAS: triggering myoblast fusion in Drosophila. Dev Dyn 238, 1513-25.
15. Schafer, G., Weber, S., Holz, A., Bogdan, S., Schumacher, S., Muller, A., Renkawitz-Pohl, R., and Onel, S. F. (2007). The Wiskott-Aldrich syndrome protein (WASP) is essential for myoblast fusion in Drosophila. Dev Biol 304, 664-74.
16. Gray, S., and Levine, M. (1996). Short-range transcriptional repressors mediate both quenching and direct repression within complex loci in Drosophila. Genes Dev 10, 700-10.
17. Canon, J., and Banerjee, U. (2003). In vivo analysis of a developmental circuit for direct transcriptional activation and repression in the same cell by a Runx protein. Genes Dev 17, 838-43.
18. Jimenez, G., Paroush, Z., and Ish-Horowicz, D. (1997). Groucho acts as a corepressor for a subset of negative regulators, including Hairy and Engrailed. Genes Dev 11, 3072-82.
19. Sandmann, T., Girardot, C., Brehme, M., Tongprasit, W., Stolc, V., and Furlong, E. E. (2007). A core transcriptional network for early mesoderm development in Drosophila melanogaster. Genes Dev 21, 436-49.
20. Leptin, M. (1991). twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev 5, 1568-76.
21. Ip, Y. T., Park, R. E., Kosman, D., Yazdanbakhsh, K., and Levine, M. (1992). dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev 6, 1518-30.
22. Luo, L., Liao, Y. J., Jan, L. Y., and Jan, Y. N. (1994). Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev 8, 1787-802.
23. Ganguly, A., Jiang, J., and Ip, Y. T. (2005). Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo. Development 132, 3419-29.
24. Qiu, F., Brendel, S., Cunha, P. M., Astola, N., Song, B., Furlong, E. E., Leonard, K. R., and Bullard, B. (2005). Myofilin, a protein in the thick filaments of insect muscle. J Cell Sci 118, 1527-36.
25. Sandmann, T., Jensen, L. J., Jakobsen, J. S., Karzynski, M. M., Eichenlaub, M. P., Bork, P., and Furlong, E. E. (2006b). A temporal map of transcription factor activity: mef2 directly regulates target genes at all stages of muscle development. Dev Cell 10, 797-807.
26. Metabotropic glutamate and dopamine receptors co-regulate AMPA receptor activity through PKA in cultured chick retinal neurones: effect on GluR4 phosphorylation and surface expression.
27. Rubin, G. M., and Lewis, E. B. (2000). A brief history of Drosophila's contributions to genome research. Science 287, 2216-8.
28. Drosophila D-titin is required for myoblast fusion and skeletal muscle striation. J Cell Sci 113 ( Pt 17), 3103-15.
29. Clark, A. G., et al. (2007). Evolution of genes and genomes on the Drosophila phylogeny. Nature 450, 203-18.
30. Kim, S., Shilagardi, K., Zhang, S., Hong, S. N., Sens, K. L., Bo, J., Gonzalez, G. A., and Chen, E. H. (2007). A critical function for the actin cytoskeleton in targeted exocytosis of prefusion vesicles during myoblast fusion. Dev Cell 12, 571-86.
31. Chen, E. H., and Olson, E. N. (2001). Antisocial, an intracellular adaptor protein, is required for myoblast fusion in Drosophila. Dev Cell 1, 705-15.
32. Bourgouin, C., Lundgren, S. E., and Thomas, J. B. (1992). Apterous is a Drosophila LIM domain gene required for the development of a subset of embryonic muscles. Neuron 9, 549-61.
33. Furlong, E. E., Profitt, D., and Scott, M. P. (2001b). Automated sorting of live transgenic embryos. Nat Biotechnol 19, 153-6.
34. Schroter, R. H., Buttgereit, D., Beck, L., Holz, A., and Renkawitz-Pohl, R. (2006). Blown fuse regulates stretching and outgrowth but not myoblast fusion of the circular visceral muscles in Drosophila. Differentiation 74, 608-21.
35. Turner, B. M. (2002). Cellular memory and the histone code. Cell 111, 285-91. REFERENCES 131
36. Sandmann, T., Jakobsen, J. S., and Furlong, E. E. (2006a). ChIP-on-chip protocol for genome-wide analysis of transcription factor binding in Drosophila melanogaster embryos. Nat Protoc 1, 2839-55.
37. Hummel, T., Schimmelpfeng, K., and Klambt, C. (1999). Commissure formation in the embryonic CNS of Drosophila. Dev Biol 209, 381-98.
38. Taylor, M. V. (2006). Comparison of muscle development in drosophila and vertebrates. In "Muscle development in drosophila" (H. Sink, Ed.), pp. 207. Landes Bioscience/Eurekah.com ; Springer Science + Business Media, Georgetown, Tex. New York, N.Y.
39. Riechmann, V., Irion, U., Wilson, R., Grosskortenhaus, R., and Leptin, M. (1997). Control of cell fates and segmentation in the Drosophila mesoderm. Development 124, 2915-22.
40. Chen, E. H., Pryce, B. A., Tzeng, J. A., Gonzalez, G. A., and Olson, E. N. (2003). Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Cell 114, 751-62.
41. Molkentin, J. D., Black, B. L., Martin, J. F., and Olson, E. N. (1995). Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell 83, 1125-36.
42. Jia, J., and Jiang, J. (2006). Decoding the Hedgehog signal in animal development. Cell Mol Life Sci 63, 1249-65.
43. Gilbert, S. F. (2006). "Developmental biology." Sinauer Associates Inc. Publishers, Sunderland, Mass.
44. Lin, S. C., and Storti, R. V. (1997). Developmental regulation of the Drosophila Tropomyosin I (TmI) gene is controlled by a muscle activator enhancer region that contains multiple cis-elements and binding sites for multiple proteins. Dev Genet 20, 297-306.
45. Stathopoulos, A., and Levine, M. (2002). Dorsal gradient networks in the Drosophila embryo. Dev Biol 246, 57-67.
46. Staehling-Hampton, K., Hoffmann, F. M., Baylies, M. K., Rushton, E., and Bate, M. (1994). dpp induces mesodermal gene expression in Drosophila. Nature 372, 783-6.
47. Duan, H., Skeath, J. B., and Nguyen, H. T. (2001). Drosophila Lame duck, a novel member of the Gli superfamily, acts as a key regulator of myogenesis by controlling fusion-competent myoblast development. Development 128, 4489-500.
48. Bour, B. A., O'Brien, M. A., Lockwood, W. L., Goldstein, E. S., Bodmer, R., Taghert, P. H., Abmayr, S. M., and Nguyen, H. T. (1995). Drosophila MEF2, a transcription factor that is essential for myogenesis. Genes Dev 9, 730-41.
49. Nguyen, H. T., and Xu, X. (1998). Drosophila mef2 expression during mesoderm development is controlled by a complex array of cis-acting regulatory modules. Dev Biol 204, 550-66.
50. Kelly, K. K., Meadows, S. M., and Cripps, R. M. (2002). Drosophila MEF2 is a direct regulator of Actin57B transcription in cardiac, skeletal, and visceral muscle lineages. Mech Dev 110, 39-50.
51. Bour, B. A., Chakravarti, M., West, J. M., and Abmayr, S. M. (2000). Drosophila SNS, a member of the immunoglobulin superfamily that is essential for myoblast fusion. Genes Dev 14, 1498-511.
52. Davis, R. L., Weintraub, H., and Lassar, A. B. (1987). Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987-1000.
53. Sims, D., Bursteinas, B., Gao, Q., Zvelebil, M., and Baum, B. (2006). FLIGHT: database and tools for the integration and cross-correlation of large-scale RNAi phenotypic datasets. Nucleic Acids Res 34, D479-83.
54. Paulo M. F. Cunha*, Thomas Sandmann*, E. Hilary Gustafson, Lucia Ciglar, Michael P. Eichenlaub, Eileen E.M. Furlong * These authors contributed equally Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue- specific modulator of Mef2 activity PLoS Genetics (In revision).
55. Barolo, S., Carver, L. A., and Posakony, J. W. (2000). GFP and beta-galactosidase transformation vectors for promoter/enhancer analysis in Drosophila. Biotechniques 29, 726, 728, 730, 732.
56. Blackwood, E. M., and Kadonaga, J. T. (1998). Going the distance: a current view of enhancer action. Science 281, 61-3.
57. Rudnicki, M. A., Braun, T., Hinuma, S., and Jaenisch, R. (1992). Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell 71, 383-90.
58. Damm, C., Wolk, A., Buttgereit, D., Loher, K., Wagner, E., Lilly, B., Olson, E. N., Hasenpusch-Theil, K., and Renkawitz-Pohl, R. (1998). Independent regulatory elements in the upstream region of the Drosophila beta 3 tubulin gene (beta Tub60D) guide expression in the dorsal vessel and the somatic muscles. Dev Biol 199, 138-49.
59. Frasch, M. (1995). Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo. Nature 374, 464-7.
60. Schroter, R. H., Lier, S., Holz, A., Bogdan, S., Klambt, C., Beck, L., and Renkawitz-Pohl, R. (2004). kette and blown fuse interact genetically during the second fusion step of myogenesis in Drosophila. Development 131, 4501-9.
61. Balagopalan, L., Keller, C. A., and Abmayr, S. M. (2001). Loss-of-function mutations reveal that the Drosophila nautilus gene is not essential for embryonic myogenesis or viability. Dev Biol 231, 374-82.
62. Morin, S., Pozzulo, G., Robitaille, L., Cross, J., and Nemer, M. (2005). MEF2- dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. J Biol Chem 280, 32272-8.
63. Keller, C. A., Erickson, M. S., and Abmayr, S. M. (1997). Misexpression of nautilus induces myogenesis in cardioblasts and alters the pattern of somatic muscle fibers. Dev Biol 181, 197-212.
64. Vigoreaux, J. O. (2006). Molecular basis of muscle structure. In "Muscle development in drosophila" (H. Sink, Ed.), pp. 207. Landes Bioscience/Eurekah.com ; Springer Science + Business Media, Georgetown, Tex. New York, N.Y.
65. Kassar-Duchossoy, L., Gayraud-Morel, B., Gomes, D., Rocancourt, D., Buckingham, M., Shinin, V., and Tajbakhsh, S. (2004). Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature 431, 466-71.
66. Wang, G., and Jiang, J. (2004). Multiple Cos2/Ci interactions regulate Ci subcellular localization through microtubule dependent and independent mechanisms. Dev Biol 268, 493-505.
67. Volk, T. (2006). Muscle attachment sites: where migrating muscles meet their match. In "Muscle development in drosophila" (H. Sink, Ed.), pp. 207. Landes Bioscience/Eurekah.com ; Springer Science + Business Media, Georgetown, Tex. New York, N.Y.
68. Hasty, P., Bradley, A., Morris, J. H., Edmondson, D. G., Venuti, J. M., Olson, E. N., and Klein, W. H. (1993). Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature 364, 501-6.
69. Kesper, D. A., Stute, C., Buttgereit, D., Kreiskother, N., Vishnu, S., Fischbach, K. F., and Renkawitz-Pohl, R. (2007). Myoblast fusion in Drosophila melanogaster is mediated through a fusion-restricted myogenic-adhesive structure (FuRMAS). Dev Dyn 236, 404-15.
70. Ruiz-Gomez, M., Coutts, N., Suster, M. L., Landgraf, M., and Bate, M. (2002). myoblasts incompetent encodes a zinc finger transcription factor required to specify fusion-competent myoblasts in Drosophila. Development 129, 133-41.
71. Berkes, C. A., and Tapscott, S. J. (2005). MyoD and the transcriptional control of myogenesis. Semin Cell Dev Biol 16, 585-95.
72. Rudnicki, M. A., Schnegelsberg, P. N., Stead, R. H., Braun, T., Arnold, H. H., and Jaenisch, R. (1993). MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75, 1351-9.
73. Baylies, M. K., Bate, M., and Ruiz Gomez, M. (1998). Myogenesis: a view from Drosophila. Cell 93, 921-7.
74. Nicholson, L., and Keshishian, H. (2006). Neuromuscular development: connectivity and plasticity. In "Muscle development in drosophila" (H. Sink, Ed.), pp. 207. Landes Bioscience/Eurekah.com ; Springer Science + Business Media, Georgetown, Tex.
75. Furlong, E. E., Andersen, E. C., Null, B., White, K. P., and Scott, M. P. (2001a). Patterns of gene expression during Drosophila mesoderm development. Science 293, 1629-33.
76. Cripps, R. M., Lovato, T. L., and Olson, E. N. (2004). Positive autoregulation of the Myocyte enhancer factor-2 myogenic control gene during somatic muscle development in Drosophila. Dev Biol 267, 536-47.
77. Hakeda-Suzuki, S., Ng, J., Tzu, J., Dietzl, G., Sun, Y., Harms, M., Nardine, T., Luo, L., and Dickson, B. J. (2002). Rac function and regulation during Drosophila development. Nature 416, 438-42.
78. Carmena, A., Buff, E., Halfon, M. S., Gisselbrecht, S., Jimenez, F., Baylies, M. K., and Michelson, A. M. (2002). Reciprocal regulatory interactions between the Notch and Ras signaling pathways in the Drosophila embryonic mesoderm. Dev Biol 244, 226-42.
79. Olson, E. N., Perry, M., and Schulz, R. A. (1995). Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors. Dev Biol 172, 2-14.
80. Lilly, B., Zhao, B., Ranganayakulu, G., Paterson, B. M., Schulz, R. A., and Olson, E. N. (1995). Requirement of MADS domain transcription factor D-MEF2 for muscle formation in Drosophila. Science 267, 688-93.
81. Rau, A., Buttgereit, D., Holz, A., Fetter, R., Doberstein, S. K., Paululat, A., Staudt, N., Skeath, J., Michelson, A. M., and Renkawitz-Pohl, R. (2001). rolling pebbles (rols) is required in Drosophila muscle precursors for recruitment of myoblasts for fusion. Development 128, 5061-73.
82. Strunkelnberg, M., Bonengel, B., Moda, L. M., Hertenstein, A., de Couet, H. G., Ramos, R. G., and Fischbach, K. F. (2001). rst and its paralogue kirre act redundantly during embryonic muscle development in Drosophila. Development 128, 4229-39.
83. Kramer, S. G., Kidd, T., Simpson, J. H., and Goodman, C. S. (2001). Switching repulsion to attraction: changing responses to slit during transition in mesoderm migration. Science 292, 737-40.
84. Braun, T., Rudnicki, M. A., Arnold, H. H., and Jaenisch, R. (1992). Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell 71, 369-82.
85. Stute, C. (2004). The determination of the founder and fusion competent myoblasts of the visceral mesoderm of Drosophila melanogaster depends on Notch as well as on Jeb/Alk mediated RTK-signalling. Universität Marburg, Marburg.
86. Wray, G. A., Hahn, M. W., Abouheif, E., Balhoff, J. P., Pizer, M., Rockman, M. V., and Romano, L. A. (2003). The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20, 1377-419.
87. O'Neill, L. A. (2000). The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2000, RE1.
88. Hartenstein, V. (2006). The muscle pattern of drosophila. In "Muscle development in drosophila" (H. Sink, Ed.), pp. 207. Landes Bioscience/Eurekah.com ; REFERENCES 127
89. Davidson, E. H. (2006). "The regulatory genome : gene regulatory networks in development and evolution." Elsevier/Academic Press, Amsterdam ; London.
90. Kremser, T., Gajewski, K., Schulz, R. A., and Renkawitz-Pohl, R. (1999). Tinman regulates the transcription of the beta3 tubulin gene (betaTub60D) in the dorsal vessel of Drosophila. Dev Biol 216, 327-39.
91. Black, B. L., and Olson, E. N. (1998). Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Annu Rev Cell Dev Biol 14, 167-96.
92. Baylies, M. K., and Bate, M. (1996). twist: a myogenic switch in Drosophila. Science 272, 1481-4.
93. Brugnera, E., Haney, L., Grimsley, C., Lu, M., Walk, S. F., Tosello-Trampont, A. C., Macara, I. G., Madhani, H., Fink, G. R., and Ravichandran, K. S. (2002). Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nat Cell Biol 4, 574-82.
94. Drosophila dumbfounded: a myoblast attractant essential for fusion. Cell 102, 189-98.
95. Campos-Ortega, J. A., and Hartenstein, V. (1997). "The embryonic development of Drosophila melanogaster." Springer, Berlin ; New York.
96. Zeitlinger, J., Zinzen, R. P., Stark, A., Kellis, M., Zhang, H., Young, R. A., and Levine, M. (2007). Whole-genome ChIP-chip analysis of Dorsal, Twist, and Snail suggests integration of diverse patterning processes in the Drosophila embryo. Genes Dev 21, 385-90.
97. Liotta, D., Han, J., Elgar, S., Garvey, C., Han, Z., and Taylor, M. V. (2007). The Him gene reveals a balance of inputs controlling muscle differentiation in Drosophila. Curr Biol 17, 1409-13.
98. Jakobsen, J. S., Braun, M., Astorga, J., Gustafson, E. H., Sandmann, T., Karzynski, M., Carlsson, P., and Furlong, E. E. (2007). Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network. Genes Dev 21, 2448-60.
99. Doberstein, S. K., Fetter, R. D., Mehta, A. Y., and Goodman, C. S. (1997). Genetic analysis of myoblast fusion: blown fuse is required for progression beyond the prefusion complex. J Cell Biol 136, 1249-61.
100. Erickson, M. R., Galletta, B. J., and Abmayr, S. M. (1997). Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J Cell Biol 138, 589-603.
101. Elgar, S. J., Han, J., and Taylor, M. V. (2008). mef2 activity levels differentially affect gene expression during Drosophila muscle development. Proc Natl Acad Sci U S A 105, 918-23.
102. Deng, H., Hughes, S. C., Bell, J. B., and Simmonds, A. J. (2009). Alternative requirements for Vestigial, Scalloped, and Dmef2 during muscle differentiation in Drosophila melanogaster. Mol Biol Cell 20, 256-69.
103. Peterson, B. K., Hare, E. E., Iyer, V. N., Storage, S., Conner, L., Papaj, D. R., Kurashima, R., Jang, E., and Eisen, M. B. (2009). Big genomes facilitate the comparative identification of regulatory elements. PLoS One 4, e4688.
104. Richardson, B. E., Nowak, S. J., and Baylies, M. K. (2008). Myoblast fusion in fly and vertebrates: new genes, new processes and new perspectives. Traffic 9, 1050-9.
105. Geisbrecht, E. R., Haralalka, S., Swanson, S. K., Florens, L., Washburn, M. P., and Abmayr, S. M. (2008). Drosophila ELMO/CED-12 interacts with Myoblast city to direct myoblast fusion and ommatidial organization. Dev Biol 314, 137-49.
106. Morin, S., Charron, F., Robitaille, L., and Nemer, M. (2000). GATA-dependent recruitment of MEF2 proteins to target promoters. Embo J 19, 2046-55.
107. Cripps, R. M., Black, B. L., Zhao, B., Lien, C. L., Schulz, R. A., and Olson, E. N. (1998). The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis. Genes Dev 12, 422-34.
108. Tusher VG, T. R., Chu G. (2001). Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98, 5116-5121.
109. Gossett, L. A., Kelvin, D. J., Sternberg, E. A., and Olson, E. N. (1989). A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol 9, 5022-33.
110. Lin, M. H., Nguyen, H. T., Dybala, C., and Storti, R. V. (1996). Myocyte-specific enhancer factor 2 acts cooperatively with a muscle activator region to regulate Drosophila tropomyosin gene muscle expression. Proc Natl Acad Sci U S A 93, 4623-8.
111. Gray, S., Cai, H., Barolo, S., and Levine, M. (1995). Transcriptional repression in the Drosophila embryo. Philos Trans R Soc Lond B Biol Sci 349, 257-62.
112. Lilly, B., Galewsky, S., Firulli, A. B., Schulz, R. A., and Olson, E. N. (1994). D- MEF2: a MADS box transcription factor expressed in differentiating REFERENCES 128 mesoderm and muscle cell lineages during Drosophila embryogenesis. Proc Natl Acad Sci U S A 91, 5662-6.
113. Nguyen, H. T., Bodmer, R., Abmayr, S. M., McDermott, J. C., and Spoerel, N. A. (1994). D-mef2: a Drosophila mesoderm-specific MADS box-containing gene with a biphasic expression profile during embryogenesis. Proc Natl Acad Sci U S A 91, 7520-4.
114. Richards, S., et al. (2005). Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution. Genome Res 15, 1-18.
115. Menon, S. D., and Chia, W. (2001). Drosophila rolling pebbles: a multidomain protein required for myoblast fusion that recruits D-Titin in response to the myoblast attractant Dumbfounded. Dev Cell 1, 691-703.

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