臺灣博碩士論文加值系統

DNA Methylation, an epigenetic mechanism, involved in the regulation of gene expression had been corrected with transcriptional repression. It is believed that through the recognition of the 5-methyl CpG dinucleotides by a conserved family of proteins, the methyl-CpG-binding-domain protein (MBD) family, the repressive effects of DNA methylation was formed.
According to the recent studies, we have known that dSETDB1 is a MBD family gene and its MBD domain specifically recognized the 5-methyl-CpG dinucleotides. In addition, dSETDB1, containing Pre-SET and bifurcated SET domains located at C terminal with respect to its MBD domain, is a Drosophila homolog of human H3-K9 histone methyltransferase, SETDB1. dSETDB1, like other genes of MBD family, act as a transcription repressor, exerts the repression through HDAC-independent pathway.
In this study, we demonstrated that dSETDB1 gene encoded a four kilobase transcript and the recessive lethality from pupal to adult stage was caused by the P-element insertion of dSETDB1 gene. We also found that pupae from homozygous mutant flies with deficiency of dSETDB1 displayed rough eye, melanotic masses, abnormal abdomen segmentation, thorax closure, atypical patterns of bristle distribution and the derived larvae showed brown branches of tracheas, indicating dSETDB1 plays a crucial role in developmental stages.

Reference
Ballestar, E., Pile, L. A., Wassarman, D. A., Wolffe, A. P., and Wade, P. A. (2001). A Drosophila MBD family member is a transcriptional corepressor associated with specific genes. Eur J Biochem 268, 5397-5406.
Dearolf, C. R. (1998). Fruit fly "leukemia". Biochim Biophys Acta 1377, M13-23. Evans, C. J., Hartenstein, V., and Banerjee, U. (2003). Thicker than blood: conserved mechanisms in Drosophila and vertebrate hematopoiesis. Dev Cell 5, 673-690.
Evans, C. J., Hartenstein, V., and Banerjee, U. (2003). Thicker than blood: conserved mechanisms in Drosophila and vertebrate hematopoiesis. Dev Cell 5, 673-690.
Golic, K. G., and Golic, M. M. (1996). Engineering the Drosophila genome: chromosome rearrangements by design. Genetics 144, 1693-1711.
Harte, P. J., Wu, W., Carrasquillo, M. M., and Matera, A. G. (1999). Assignment of a novel bifurcated SET domain gene, SETDB1, to human chromosome band 1q21 by in situ hybridization and radiation hybrids. Cytogenet Cell Genet 84, 83-86.
Harrison, D. A., McCoon, P. E., Binari, R., Gilman, M., and Perrimon, N. (1998). Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. Genes Dev 12, 3252-3263.
Hendrich, B., and Tweedie, S. (2003). The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet 19, 269-277.
Hung, M. S., and Shen, C. K. (2003). Eukaryotic methyl-CpG-binding domain proteins and chromatin modification. Eukaryot Cell 2, 841-846.
Hou, X. S., Melnick, M. B., and Perrimon, N. (1996). Marelle acts downstream of the Drosophila HOP/JAK kinase and encodes a protein similar to the mammalian STATs. Cell 84, 411-419.
Izon, D. J., Punt, J. A., and Pear, W. S. (2002). Deciphering the role of Notch signaling in lymphopoiesis. Curr Opin Immunol 14, 192-199.
Kouzarides, T. (2002). Histone methylation in transcriptional control. Curr Opin Genet Dev 12, 198-209.
Luo, H., Hanratty, W. P., and Dearolf, C. R. (1995). An amino acid substitution in the Drosophila hopTum-l Jak kinase causes leukemia-like hematopoietic defects. Embo J 14, 1412-1420.
Luo, H., and Dearolf, C. R. (2001). The JAK/STAT pathway and Drosophila development. Bioessays 23, 1138-1147.
MacDonald, H. R., Wilson, A., and Radtke, F. (2001). Notch1 and T-cell development: insights from conditional knockout mice. Trends Immunol 22, 155-160.
Meister, M., and Lagueux, M. (2003). Drosophila blood cells. Cell Microbiol 5, 573-580.
Perrimon, N., and Mahowald, A. P. (1986). l(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila. Dev Biol 118, 28-41.
Portin, P. (2002). General outlines of the molecular genetics of the Notch signalling pathway in Drosophila melanogaster: a review. Hereditas 136, 89-96.
Schotta, G., Ebert, A., Krauss, V., Fischer, A., Hoffmann, J., Rea, S., Jenuwein, T., Dorn, R., and Reuter, G. (2002). Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. Embo J 21, 1121-1131.
Schultz, D. C., Ayyanathan, K., Negorev, D., Maul, G. G., and Rauscher, F. J., 3rd (2002). SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 16, 919-932.
Tepass, U., Fessler, L. I., Aziz, A., and Hartenstein, V. (1994). Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development 120, 1829-1837.
Wade, P. A. (2001). Methyl CpG-binding proteins and transcriptional repression. Bioessays 23, 1131-1137.
Zhang, Y., and Reinberg, D. (2001). Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev 15, 2343-2360.