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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳宏文 | |
dc.contributor.author | Ching-Yeu Liang | en |
dc.contributor.author | 梁瀞予 | zh_TW |
dc.date.accessioned | 2021-06-08T07:19:33Z | - |
dc.date.copyright | 2008-07-30 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-24 | |
dc.identifier.citation | Aapola, U., Kawasaki, K., Scott, H.S., Ollila, J., Vihinen, M., Heino, M., Shintani, A., Minoshima, S., Krohn, K., Antonarakis, S.E. (2000). Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family. Genomics 65, 293-298.
Akiyama, Y., Hosoya, T., Poole, A.M., and Hotta, Y. (1996). The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc Natl Acad Sci U S A 93, 14912-14916. Altshuller, Y., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., and Frohman, M.A. (1996). Gcm1, a mammalian homolog of Drosophila glial cells missing. FEBS Lett 393, 201-204. Anson-Cartwright, L., Dawson, K., Holmyard, D., Fisher, S.J., Lazzarini, R.A., and Cross, J.C. (2000). The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Nat Genet 25, 311-314. Antony, J.M., van Marle, G., Opii, W., Butterfield, D.A., Mallet, F., Yong, V.W., Wallace, J.L., Deacon, R.M., Warren, K., and Power, C. (2004). Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci 7, 1088-1095. Bannister, A.J., and Kouzarides, T. (1996). The CBP co-activator is a histone acetyltransferase. Nature 384, 641-643. Bernstein, B.E., Meissner, A., and Lander, E.S. (2007). The mammalian epigenome. Cell 128, 669-681. Bestor, T., Laudano, A., Mattaliano, R., and Ingram, V. (1988). Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 203, 971-983. Bhattacharya, S.K., Ramchandani, S., Cervoni, N., and Szyf, M. (1999). A mammalian protein with specific demethylase activity for mCpG DNA. Nature 397, 579-583. Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev 16, 6-21. Bird, A. (2007). Perceptions of epigenetics. Nature 447, 396-398. Black, S., Kadyrov, M., Kaufmann, P., Ugele, B., Emans, N., and Huppertz, B. (2004). Syncytial fusion of human trophoblast depends on caspase 8. Cell Death Differ 11, 90-98. Blaise, S., de Parseval, N., Benit, L., and Heidmann, T. (2003). Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci U S A 100, 13013-13018. Brandeis, M., Ariel, M., and Cedar, H. (1993). Dynamics of DNA methylation during development. Bioessays 15, 709-713. Brown, T.C., and Jiricny, J. (1988). Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell 54, 705-711. Chan, H.M., and La Thangue, N.B. (2001). p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 114, 2363-2373. Chang, C.W., Chuang, H.C., Yu, C., Yao, T.P., and Chen, H. (2005). Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa. Mol Cell Biol 25, 8401-8414. Chang, M., Mukherjea, D., Gobble, R.M., Groesch, K.A., Torry, R.J., and Torry, D.S. (2008). Glial cell missing 1 regulates placental growth factor (PGF) gene transcription in human trophoblast. Biol Reprod 78, 841-851. Chapman, V., Forrester, L., Sanford, J., Hastie, N., and Rossant, J. (1984). Cell lineage-specific undermethylation of mouse repetitive DNA. Nature 307, 284-286. Chen, C.P., Chen, C.Y., Yang, Y.C., Su, T.H., and Chen, H. (2004). Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia. Placenta 25, 413-421. Cohen, S.X., Moulin, M., Hashemolhosseini, S., Kilian, K., Wegner, M., and Muller, C.W. (2003). Structure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition. EMBO J 22, 1835-1845. Cohen, S.X., Moulin, M., Schilling, O., Meyer-Klaucke, W., Schreiber, J., Wegner, M., and Muller, C.W. (2002). The GCM domain is a Zn-coordinating DNA-binding domain. FEBS Lett 528, 95-100. de Parseval, N., Lazar, V., Casella, J.F., Benit, L., and Heidmann, T. (2003). Survey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins. J Virol 77, 10414-10422. Dong, A., Yoder, J.A., Zhang, X., Zhou, L., Bestor, T.H., and Cheng, X. (2001). Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA. Nucleic Acids Res 29, 439-448. Eden, A., Gaudet, F., Waghmare, A., and Jaenisch, R. (2003). Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300, 455. Frank, D., Keshet, I., Shani, M., Levine, A., Razin, A., and Cedar, H. (1991). Demethylation of CpG islands in embryonic cells. Nature 351, 239-241. Fuks, F., Burgers, W.A., Godin, N., Kasai, M., and Kouzarides, T. (2001). Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J 20, 2536-2544. Goll, M.G., Kirpekar, F., Maggert, K.A., Yoder, J.A., Hsieh, C.L., Zhang, X., Golic, K.G., Jacobsen, S.E., and Bestor, T.H. (2006). Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311, 395-398. Grange, T., Cappabianca, L., Flavin, M., Sassi, H., and Thomassin, H. (2001). In vivo analysis of the model tyrosine aminotransferase gene reveals multiple sequential steps in glucocorticoid receptor action. Oncogene 20, 3028-3038. Griffiths, D.J. (2001). Endogenous retroviruses in the human genome sequence. Genome Biol 2, REVIEWS1017. Hata, K., Okano, M., Lei, H., and Li, E. (2002). Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129, 1983-1993. Hemberger, M. (2007). Epigenetic landscape required for placental development. Cell Mol Life Sci 64, 2422-2436. Hermann, A., Schmitt, S., and Jeltsch, A. (2003). The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J Biol Chem 278, 31717-31721. Holliday, R., and Pugh, J.E. (1975). DNA modification mechanisms and gene activity during development. Science 187, 226-232. Hosoya, T., Takizawa, K., Nitta, K., and Hotta, Y. (1995). glial cells missing: a binary switch between neuronal and glial determination in Drosophila. Cell 82, 1025-1036. Huppertz, B., Bartz, C., and Kokozidou, M. (2006). Trophoblast fusion: fusogenic proteins, syncytins and ADAMs, and other prerequisites for syncytial fusion. Micron 37, 509-517. Huppertz, B., Black, S., Kaufmann, P., Po¨tgens, A., (2002). Antisense inhibition of syncytin in villous explants—a role of syncytin in trophoblast differentiation? Placenta 23, A48. Imhof, A., and Becker, P.B. (2001). Modifications of the histone N-terminal domains. Evidence for an 'epigenetic code'? Mol Biotechnol 17, 1-13. Jaenisch, R. (1997). DNA methylation and imprinting: why bother? Trends Genet 13, 323-329. Jahner, D., Stuhlmann, H., Stewart, C.L., Harbers, K., Lohler, J., Simon, I., and Jaenisch, R. (1982). De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature 298, 623-628. Jones, B.W., Fetter, R.D., Tear, G., and Goodman, C.S. (1995). glial cells missing: a genetic switch that controls glial versus neuronal fate. Cell 82, 1013-1023. Jost, J.P. (1993). Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc Natl Acad Sci U S A 90, 4684-4688. Jost, J.P., and Bruhat, A. (1997). The formation of DNA methylation patterns and the silencing of genes. Prog Nucleic Acid Res Mol Biol 57, 217-248. Jost, J.P., and Jost, Y.C. (1994). Transient DNA demethylation in differentiating mouse myoblasts correlates with higher activity of 5-methyldeoxycytidine excision repair. J Biol Chem 269, 10040-10043. Jost, J.P., Oakeley, E.J., Zhu, B., Benjamin, D., Thiry, S., Siegmann, M., and Jost, Y.C. (2001). 5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation. Nucleic Acids Res 29, 4452-4461. Kanemura, Y., Hiraga, S., Arita, N., Ohnishi, T., Izumoto, S., Mori, K., Matsumura, H., Yamasaki, M., Fushiki, S., and Yoshimine, T. (1999). Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene. FEBS Lett 442, 151-156. Kato, N., Pfeifer-Ohlsson, S., Kato, M., Larsson, E., Rydnert, J., Ohlsson, R., and Cohen, M. (1987). Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human cellular sequences. J Virol 61, 2182-2191. Kim, H.S., Yi, J.M., Hirai, H., Huh, J.W., Jeong, M.S., Jang, S.B., Kim, C.G., Saitou, N., Hyun, B.H., and Lee, W.H. (2006). Human Endogenous Retrovirus (HERV)-R family in primates: Chromosomal location, gene expression, and evolution. Gene 370, 34-42. Kim, J., Jones, B.W., Zock, C., Chen, Z., Wang, H., Goodman, C.S., and Anderson, D.J. (1998). Isolation and characterization of mammalian homologs of the Drosophila gene glial cells missing. Proc Natl Acad Sci U S A 95, 12364-12369. Kress, C., Thomassin, H., and Grange, T. (2001). Local DNA demethylation in vertebrates: how could it be performed and targeted? FEBS Lett 494, 135-140. Li, E., Bestor, T.H., and Jaenisch, R. (1992). Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915-926. Lower, R. (1999). The pathogenic potential of endogenous retroviruses: facts and fantasies. Trends Microbiol 7, 350-356. Lower, R., Lower, J., and Kurth, R. (1996). The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci U S A 93, 5177-5184. Malassine, A., Blaise, S., Handschuh, K., Lalucque, H., Dupressoir, A., Evain-Brion, D., and Heidmann, T. (2007). Expression of the fusogenic HERV-FRD Env glycoprotein (syncytin 2) in human placenta is restricted to villous cytotrophoblastic cells. Placenta 28, 185-191. Malassine, A., Frendo, J.L., Blaise, S., Handschuh, K., Gerbaud, P., Tsatsaris, V., Heidmann, T., and Evain-Brion, D. (2008). Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta. Retrovirology 5, 6. Margueron, R., Trojer, P., and Reinberg, D. (2005). The key to development: interpreting the histone code? Curr Opin Genet Dev 15, 163-176. Marin, M., Lavillette, D., Kelly, S.M., and Kabat, D. (2003). N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions. J Virol 77, 2936-2945. Marin, M., Tailor, C.S., Nouri, A., and Kabat, D. (2000). Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus. J Virol 74, 8085-8093. Matouskova, M., Blazkova, J., Pajer, P., Pavlicek, A., and Hejnar, J. (2006). CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. Exp Cell Res 312, 1011-1020. Metivier, R., Gallais, R., Tiffoche, C., Le Peron, C., Jurkowska, R.Z., Carmouche, R.P., Ibberson, D., Barath, P., Demay, F., Reid, G., et al. (2008). Cyclical DNA methylation of a transcriptionally active promoter. Nature 452, 45-50. Mi, S., Lee, X., Li, X., Veldman, G.M., Finnerty, H., Racie, L., LaVallie, E., Tang, X.Y., Edouard, P., Howes, S., et al. (2000). Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785-789. Minas, V., Loutradis, D., and Makrigiannakis, A. (2005). Factors controlling blastocyst implantation. Reprod Biomed Online 10, 205-216. Ng, H.H., and Bird, A. (1999). DNA methylation and chromatin modification. Curr Opin Genet Dev 9, 158-163. Oakeley, E.J., and Jost, J.P. (1996). Non-symmetrical cytosine methylation in tobacco pollen DNA. Plant Mol Biol 31, 927-930. Okahara, G., Matsubara, S., Oda, T., Sugimoto, J., Jinno, Y., and Kanaya, F. (2004). Expression analyses of human endogenous retroviruses (HERVs): tissue-specific and developmental stage-dependent expression of HERVs. Genomics 84, 982-990. Okano, M., Bell, D.W., Haber, D.A., and Li, E. (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257. Okano, M., Xie, S., and Li, E. (1998). Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19, 219-220. Perron, H., Lalande, B., Gratacap, B., Laurent, A., Genoulaz, O., Geny, C., Mallaret, M., Schuller, E., Stoebner, P., and Seigneurin, J.M. (1991). Isolation of retrovirus from patients with multiple sclerosis. Lancet 337, 862-863. Posfai, J., Bhagwat, A.S., Posfai, G., and Roberts, R.J. (1989). Predictive motifs derived from cytosine methyltransferases. Nucleic Acids Res 17, 2421-2435. Pray-Grant, M.G., Daniel, J.A., Schieltz, D., Yates, J.R., 3rd, and Grant, P.A. (2005). Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation. Nature 433, 434-438. Ramsahoye, B.H., Biniszkiewicz, D., Lyko, F., Clark, V., Bird, A.P., and Jaenisch, R. (2000). Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci U S A 97, 5237-5242. Razin, A. (1998). CpG methylation, chromatin structure and gene silencing-a three-way connection. EMBO J 17, 4905-4908. Reiss, D., Zhang, Y., and Mager, D.L. (2007). Widely variable endogenous retroviral methylation levels in human placenta. Nucleic Acids Res 35, 4743-4754. Rigaud, G., Roux, J., Pictet, R., and Grange, T. (1991). In vivo footprinting of rat TAT gene: dynamic interplay between the glucocorticoid receptor and a liver-specific factor. Cell 67, 977-986. Riggs, A.D. (1975). X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14, 9-25. Rossant, J., Sanford, J.P., Chapman, V.M., and Andrews, G.K. (1986). Undermethylation of structural gene sequences in extraembryonic lineages of the mouse. Dev Biol 117, 567-573. Sassi, H., Pictet, R., and Grange, T. (1998). Glucocorticoids are insufficient for neonatal gene induction in the liver. Proc Natl Acad Sci U S A 95, 5621-5625. Schreiber, J., Riethmacher-Sonnenberg, E., Riethmacher, D., Tuerk, E.E., Enderich, J., Bosl, M.R., and Wegner, M. (2000). Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa. Mol Cell Biol 20, 2466-2474. Schubert, S.W., Lamoureux, N., Kilian, K., Klein-Hitpass, L., and Hashemolhosseini, S. (2008). Identification of integrin-alpha4, Rb1, and syncytin a as murine placental target genes of the transcription factor GCMa/Gcm1. J Biol Chem 283, 5460-5465. Siedlecki, P., and Zielenkiewicz, P. (2006). Mammalian DNA methyltransferases. Acta Biochim Pol 53, 245-256. Simister, N.E., Story, C.M., Chen, H.L., and Hunt, J.S. (1996). An IgG-transporting Fc receptor expressed in the syncytiotrophoblast of human placenta. Eur J Immunol 26, 1527-1531. Sims, R.J., 3rd, Chen, C.F., Santos-Rosa, H., Kouzarides, T., Patel, S.S., and Reinberg, D. (2005). Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains. J Biol Chem 280, 41789-41792. Story, C.M., Mikulska, J.E., and Simister, N.E. (1994). A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus. J Exp Med 180, 2377-2381. Thomassin, H., Flavin, M., Espinas, M.L., and Grange, T. (2001). Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J 20, 1974-1983. Tini, M., Benecke, A., Um, S.J., Torchia, J., Evans, R.M., and Chambon, P. (2002). Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription. Mol Cell 9, 265-277. Tuerk, E.E., Schreiber, J., and Wegner, M. (2000). Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb. J Biol Chem 275, 4774-4782. Tweedie, S., Charlton, J., Clark, V., and Bird, A. (1997). Methylation of genomes and genes at the invertebrate-vertebrate boundary. Mol Cell Biol 17, 1469-1475. Villar-Garea, A., Fraga, M.F., Espada, J., and Esteller, M. (2003). Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res 63, 4984-4989. Walsh, C.P., Chaillet, J.R., and Bestor, T.H. (1998). Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet 20, 116-117. Wilkinson, D.A., Goodchild, N.L., Saxton, T.M., Wood, S., and Mager, D.L. (1993). Evidence for a functional subclass of the RTVL-H family of human endogenous retrovirus-like sequences. J Virol 67, 2981-2989. Yamada, K., Ogawa, H., Honda, S., Harada, N., and Okazaki, T. (1999). A GCM motif protein is involved in placenta-specific expression of human aromatase gene. J Biol Chem 274, 32279-32286. Yi, J.M., Kim, H.M., and Kim, H.S. (2006). Human endogenous retrovirus HERV-H family in human tissues and cancer cells: expression, identification, and phylogeny. Cancer Lett 231, 228-239. Yoder, J.A., and Bestor, T.H. (1998). A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Hum Mol Genet 7, 279-284. Yoder, J.A., Soman, N.S., Verdine, G.L., and Bestor, T.H. (1997). DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J Mol Biol 270, 385-395. Yu, C., Shen, K., Lin, M., Chen, P., Lin, C., Chang, G.D., and Chen, H. (2002). GCMa regulates the syncytin-mediated trophoblastic fusion. J Biol Chem 277, 50062-50068. Zhu, B., Zheng, Y., Hess, D., Angliker, H., Schwarz, S., Siegmann, M., Thiry, S., and Jost, J.P. (2000). 5-methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex. Proc Natl Acad Sci U S A 97, 5135-5139. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26658 | - |
dc.description.abstract | Syncytin 2屬於人類內生性反轉錄病毒(human endogenous retrovirus)HERV-FRD之外鞘蛋白,其專一表現在胎盤滋養層細胞中,已知syncytin 2會促進細胞滋養層細胞進行細胞融合,而形成融合滋養層,故syncytin 2在胎盤發育上扮演重要的角色。而過去研究指出,人類胚胎發育過程中,胎盤組織裡的DNA甲基化程度明顯較胚胎本體組織來的低,且最近有報導發現,syncytin家族另一個成員syncytin 1,在胎盤細胞中,syncytin 1之5’-long terminal repeat(5’-LTR)啟動子上DNA甲基化程度非常低,使得syncytin 1能表現於胎盤細胞中,因此,本篇論文想探討是否細胞能透過改變5’LTR啟動子上DNA甲基化與組蛋白修飾等後基因修飾,而達到syncytin 2表現。實驗結果顯示,胎盤細胞或組織中的syncytin 2 5’LTR上甲基化程度顯著比非胎盤細胞來的低,且5’LTR上的組蛋白修飾皆為活化態的修飾,接著再利用報導基因方式發現syncytin 2 5’LTR若甲激化會影響到其轉錄活性,但有趣的是,含DNA甲基化syncytin 2 5’LTR的報導基因送胎盤細胞中,仍具有一定的轉錄活性,這表示胎盤細胞中具有特殊分子機制可對syncytin 2 5’LTR做去甲基化的動作;接著,發現胎盤組織特定轉錄因子GCMa可調控syncytin 2表現,且在非胎盤細胞MCF-7中表現GCMa後,會促進syncytin 2 5’LTR的DNA去甲基化,故GCMa轉錄因子除了調控基因表現外,同時在syncytin 2 5'LTR啟動子的去甲基化扮演重要角色;最後發現GCMa會與thymine DNA glycosylase(TDG)之間有結合能力,而TDG過去被指出可進行DNA去甲基化的酵素,因此GCMa可能透過吸引TDG至syncytin 2 5’LTR來進行DNA去甲基化的動作。綜合以上實驗結果,證實在胎盤細胞及非胎盤細胞中,syncytin 2 5’LTR上的後基因修飾有所不同,且胎盤特殊轉錄因子GCMa可促進syncytin 2 5’LTR DNA去甲基化以及啟動syncytin 2 mRNA表現。 | zh_TW |
dc.description.abstract | Syncytin 2, an envelope glycoprotein encoded by the human endogenous retrovirus FRD (HERV-FRD), is specifically expressed in placental trophoblasts. It has been reported that syncytin 2 is a fusogenic protein. Therefore, syncytin 2 may play an important role in placental development by regulation of trophoblastic fusion. Previous studies have shown that the placenta exhibits lower overall DNA methylation levels than the embryo. A recent study has shown that the 5’-long terminal repeat (5’LTR) promoter of syncytin 1, which encodes the envelope protein of HERV-W, is hypomehtylated and controls syncytin 1 expression in placenta.
In this study, we further investigated whether DNA methylation and histone modification control syncytin 2 expression in placenta. We demonstrated that the 5’LTR of syncytin 2 is hypomethylated and harbors active histone modification in placental cells. In luciferase reporter assay, in vitro DNA methylation inhibited the promoter activity of syncytin 2 5’LTR. Interestingly, the promoter activity of in vitro methylated syncytin 2 5’LTR could be restored in placental cells. To study the mechanism that counteracts the suppressive effect of DNA methylation on syncytin 2 5’LTR promoter in placenta, we demonstrated that placental transcription factor, GCMa, not only regulates syncytin 2 expression but also promotes DNA demethylation on syncytin 2 5’LTR. We further demonstrated that GCMa associates with TDG, an enzyme that involves in DNA demethylation process. This implies that GCMa may recruit TDG to demethylate syncytin 2 5’LTR. Overall, our results reveal an epigenetic regulation of syncytin 2 gene expression and that GCMa is a key factor for DNA demethylation of syncytin 2 promoter and transcription activation of syncytin 2. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T07:19:33Z (GMT). No. of bitstreams: 1 ntu-97-R95b46014-1.pdf: 860497 bytes, checksum: 60fce310187f073bf81cdd229f5c3f22 (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 目錄………………………………………………………………….…………………I
中文摘要…………………………………………………….………………..……...III 英文摘要…………………………………………………….……………………….IV 第一章 緒論 1. 胎盤 1.1 人類胎盤發育…………………………………………………………….1 1.2 胎盤功能………………………………………………………………….3 2. 後基因調控 2.1 簡介……………………………………………………………………….4 2.2去氧核糖酸甲基化………………………………………………….…….4 2.3 DNA methyltransferases………………………………………………..5 2.4 去氧核糖酸去甲基化……………………………………………………7 2.5 組蛋白修飾………………………………………………………………8 3. 人類內生性反轉錄病毒 3.1 簡介……………………………………………………………………….9 3.2 syncytin…………………………………………………………………10 4. gcm轉錄因子………………………………………………………………...12 5. 研究動機……………………………………………………………………14 第二章 材料與方法…………………………………………………………………15 第三章 結果 1. syncytin 2 5’LTR啟動子之DNA甲基化狀態...............................................25 2. syncytin 2 5’LTR啟動子上組蛋白修飾.........................................................26 3. 核酸甲基化對syncytin 2 5’LTR轉錄活性之影響………………………….26 4. GCMa調控syncytin2表現並促進syncytin 2 5’LTR區域的去甲基化…..28 5. GCMa在細胞中會與TDG作結合…………………………………………29 第四章 討論…………………………………………………………………………31 第五章 圖表…………………………………………………………………………35 第六章 參考文獻……………………………………………………………………42 | |
dc.language.iso | zh-TW | |
dc.title | 人類胎盤融合蛋白syncytin 2後基因調控機制之探討 | zh_TW |
dc.title | Epigenetic Regulation of the Placental Fusogenic Protein, Syncytin2 | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張震東,黃銓珍,李明亭,張功耀 | |
dc.subject.keyword | 後基因,胎盤,人類融合胎盤蛋白,去氧核醣核酸甲基化,組蛋白修飾, | zh_TW |
dc.subject.keyword | epigenetics,syncytin,DNA methylation,GCMa,TDG,histone modification, | en |
dc.relation.page | 51 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2008-07-26 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科學研究所 | zh_TW |
顯示於系所單位: | 生化科學研究所 |
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檔案 | 大小 | 格式 | |
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ntu-97-1.pdf 目前未授權公開取用 | 840.33 kB | Adobe PDF |
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