請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6814完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 施修明(Hsiu-Ming Shih) | |
| dc.contributor.author | Tien-Chi Huang | en |
| dc.contributor.author | 黃天祺 | zh_TW |
| dc.date.accessioned | 2021-05-17T09:18:41Z | - |
| dc.date.available | 2017-09-18 | |
| dc.date.available | 2021-05-17T09:18:41Z | - |
| dc.date.copyright | 2012-09-18 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-12 | |
| dc.identifier.citation | References
1. Salomoni, P. and A.F. Khelifi, Daxx: death or survival protein? Trends Cell Biol, 2006. 16(2): p. 97-104. 2. Yang, X., et al., Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell, 1997. 89(7): p. 1067-76. 3. Wu, S., H.N. Loke, and A. Rehemtulla, Ultraviolet radiation-induced apoptosis is mediated by Daxx. Neoplasia, 2002. 4(6): p. 486-92. 4. Perlman, R., et al., TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation. Nat Cell Biol, 2001. 3(8): p. 708-14. 5. Michaelson, J.S., et al., Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development. Genes Dev, 1999. 13(15): p. 1918-23. 6. Michaelson, J.S. and P. Leder, RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX. J Cell Sci, 2003. 116(Pt 2): p. 345-52. 7. Zhong, S., et al., Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis. J Exp Med, 2000. 191(4): p. 631-40. 8. Ishov, A.M., et al., PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol, 1999. 147(2): p. 221-34. 9. Lin, D.Y., et al., Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell, 2006. 24(3): p. 341-54. 10. Li, H., et al., Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol, 2000. 20(5): p. 1784-96. 11. Lehembre, F., et al., Regulation of Pax3 transcriptional activity by SUMO-1-modified PML. Oncogene, 2001. 20(1): p. 1-9. 12. Nefkens, I., et al., Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 and 25 differently. J Cell Sci, 2003. 116(Pt 3): p. 513-24. 13. Hollenbach, A.D., et al., Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci, 2002. 115(Pt 16): p. 3319-30. 14. Xue, Y., et al., The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies. Proc Natl Acad Sci U S A, 2003. 100(19): p. 10635-40. 15. Ishov, A.M., O.V. Vladimirova, and G.G. Maul, Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J Cell Sci, 2004. 117(Pt 17): p. 3807-20. 16. Drane, P., et al., The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. Genes Dev, 2010. 24(12): p. 1253-65. 17. Goldberg, A.D., et al., Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell, 2010. 140(5): p. 678-91. 18. Pluta, A.F., W.C. Earnshaw, and I.G. Goldberg, Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death. J Cell Sci, 1998. 111 ( Pt 14): p. 2029-41. 19. Lalioti, V.S., et al., The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1. J Biol Chem, 2002. 277(22): p. 19783-91. 20. Ko, Y.G., et al., Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm. J Biol Chem, 2001. 276(42): p. 39103-6. 21. Charette, S.J., et al., Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol, 2000. 20(20): p. 7602-12. 22. Jung, Y.S., et al., Physical interactions and functional coupling between Daxx and sodium hydrogen exchanger 1 in ischemic cell death. J Biol Chem, 2008. 283(2): p. 1018-25. 23. Junn, E., et al., Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc Natl Acad Sci U S A, 2005. 102(27): p. 9691-6. 24. Puto, L.A. and J.C. Reed, Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation. Genes Dev, 2008. 22(8): p. 998-1010. 25. Muromoto, R., et al., Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1. J Immunol, 2004. 172(5): p. 2985-93. 26. Li, R., et al., EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene, 2000. 19(6): p. 745-53. 27. Emelyanov, A.V., et al., The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells. J Biol Chem, 2002. 277(13): p. 11156-64. 28. Kim, E.J., J.S. Park, and S.J. Um, Identification of Daxx interacting with p73, one of the p53 family, and its regulation of p53 activity by competitive interaction with PML. Nucleic Acids Res, 2003. 31(18): p. 5356-67. 29. Zhao, L.Y., et al., Negative regulation of p53 functions by Daxx and the involvement of MDM2. J Biol Chem, 2004. 279(48): p. 50566-79. 30. Lin, D.Y., et al., Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering Daxx to the PML oncogenic domains (PODs) to enhance its transactivation potential. J Biol Chem, 2003. 278(18): p. 15958-65. 31. Lin, D.Y., et al., Negative modulation of androgen receptor transcriptional activity by Daxx. Mol Cell Biol, 2004. 24(24): p. 10529-41. 32. Chang, C.C., et al., Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4. J Biol Chem, 2005. 280(11): p. 10164-73. 33. Muromoto, R., et al., Physical and functional interactions between Daxx and STAT3. Oncogene, 2006. 25(14): p. 2131-6. 34. Croxton, R., et al., Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB. Cancer Res, 2006. 66(18): p. 9026-35. 35. Park, J., et al., Inhibition of NF-kappaB acetylation and its transcriptional activity by Daxx. J Mol Biol, 2007. 368(2): p. 388-97. 36. Huang, Y.S. and H.M. Shih, Daxx positively modulates beta-catenin/TCF4-mediated transcriptional potential. Biochem Biophys Res Commun, 2009. 386(4): p. 762-8. 37. Shih, H.M., et al., Daxx mediates SUMO-dependent transcriptional control and subnuclear compartmentalization. Biochem Soc Trans, 2007. 35(Pt 6): p. 1397-400. 38. Lindsay, C.R., V.M. Morozov, and A.M. Ishov, PML NBs (ND10) and Daxx: from nuclear structure to protein function. Front Biosci, 2008. 13: p. 7132-42. 39. Tang, J., et al., Critical role for Daxx in regulating Mdm2. Nat Cell Biol, 2006. 8(8): p. 855-62. 40. Michod, D., et al., Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation. Neuron, 2012. 74(1): p. 122-35. 41. Lewis, P.W., et al., Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc Natl Acad Sci U S A, 2010. 107(32): p. 14075-80. 42. Akterin, S., et al., Involvement of glutaredoxin-1 and thioredoxin-1 in beta-amyloid toxicity and Alzheimer's disease. Cell Death Differ, 2006. 13(9): p. 1454-65. 43. Jiao, Y., et al., DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science, 2011. 331(6021): p. 1199-203. 44. Heaphy, C.M., et al., Altered telomeres in tumors with ATRX and DAXX mutations. Science, 2011. 333(6041): p. 425. 45. Carninci, P., et al., The transcriptional landscape of the mammalian genome. Science, 2005. 309(5740): p. 1559-63. 46. Wang, K.C. and H.Y. Chang, Molecular mechanisms of long noncoding RNAs. Mol Cell, 2011. 43(6): p. 904-14. 47. Bertone, P., et al., Global identification of human transcribed sequences with genome tiling arrays. Science, 2004. 306(5705): p. 2242-6. 48. Ponjavic, J., C.P. Ponting, and G. Lunter, Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res, 2007. 17(5): p. 556-65. 49. Struhl, K., Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat Struct Mol Biol, 2007. 14(2): p. 103-5. 50. Guttman, M., et al., Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat Biotechnol, 2010. 28(5): p. 503-10. 51. Guttman, M., et al., Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 2009. 458(7235): p. 223-7. 52. Cabili, M.N., et al., Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev, 2011. 25(18): p. 1915-27. 53. Lee, J.T., Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev, 2009. 23(16): p. 1831-42. 54. Rinn, J.L., et al., Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 2007. 129(7): p. 1311-23. 55. Wang, K.C., et al., A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature, 2011. 472(7341): p. 120-4. 56. Guttman, M., et al., lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature, 2011. 477(7364): p. 295-300. 57. Huarte, M., et al., A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 2010. 142(3): p. 409-19. 58. Gupta, R.A., et al., Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 2010. 464(7291): p. 1071-6. 59. Loewer, S., et al., Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet, 2010. 42(12): p. 1113-7. 60. Zhao, J., et al., Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science, 2008. 322(5902): p. 750-6. 61. Nagano, T., et al., The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science, 2008. 322(5908): p. 1717-20. 62. Tsai, M.C., et al., Long noncoding RNA as modular scaffold of histone modification complexes. Science, 2010. 329(5992): p. 689-93. 63. Khalil, A.M., et al., Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A, 2009. 106(28): p. 11667-72. 64. Zhao, J., et al., Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell, 2010. 40(6): p. 939-53. 65. Kim, T.K., et al., Widespread transcription at neuronal activity-regulated enhancers. Nature, 2010. 465(7295): p. 182-7. 66. Wang, D., et al., Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature, 2011. 474(7351): p. 390-4. 67. Orom, U.A., et al., Long noncoding RNAs with enhancer-like function in human cells. Cell, 2010. 143(1): p. 46-58. 68. Mao, Y.S., B. Zhang, and D.L. Spector, Biogenesis and function of nuclear bodies. Trends Genet, 2011. 27(8): p. 295-306. 69. Clemson, C.M., et al., An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell, 2009. 33(6): p. 717-26. 70. Chen, L.L. and G.G. Carmichael, Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. Mol Cell, 2009. 35(4): p. 467-78. 71. Tripathi, V., et al., The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 2010. 39(6): p. 925-38. 72. Ishii, N., et al., Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet, 2006. 51(12): p. 1087-99. 73. Mendell, J.T. and E.N. Olson, MicroRNAs in stress signaling and human disease. Cell, 2012. 148(6): p. 1172-87. 74. Geng, Y.J., et al., Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res, 2011. 39(6): p. 2119-28. 75. Kogo, R., et al., Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res, 2011. 71(20): p. 6320-6. 76. Gibb, E.A., et al., Human cancer long non-coding RNA transcriptomes. PLoS One, 2011. 6(10): p. e25915. 77. Chang, C.C., et al., Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralog-Selective Binding and Apoptosis Modulation. Mol Cell, 2011. 42(1): p. 62-74. 78. Yap, K.L., et al., Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell, 2010. 38(5): p. 662-74. 79. Schwartzentruber, J., et al., Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature, 2012. 482(7384): p. 226-31. 80. Hermeking, H., The miR-34 family in cancer and apoptosis. Cell Death Differ, 2010. 17(2): p. 193-9. 81. Ip, J.Y. and S. Nakagawa, Long non-coding RNAs in nuclear bodies. Dev Growth Differ, 2011. 82. Mikkelsen, T.S., et al., Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature, 2007. 448(7153): p. 553-60. 83. Garcia, M.J., et al., A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes. Oncogene, 2005. 24(33): p. 5235-45. 84. Yang, Z.Q., et al., Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer. Cancer Res, 2006. 66(24): p. 11632-43. 85. Yang, Z.Q., et al., Transforming properties of 8p11-12 amplified genes in human breast cancer. Cancer Res, 2010. 70(21): p. 8487-97. 86. Holland, D.G., et al., ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med, 2011. 3(3): p. 167-80. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6814 | - |
| dc.description.abstract | Daxx 蛋白質最初被證明在細胞質內與Fas受體的凋亡區段互相結合，並扮演訊息傳遞重要的角色，然而許多報導指出，Daxx主要在細胞核內執行基因轉錄調節的功能。為了更進一步瞭解Daxx 對於基因表現的影響，本實驗利用微陣列晶片系統性的找尋Daxx調控的編碼基因(protein-coding gene) 及長非編碼RNA (large intergenic non-coding RNA)。分析結果指出當抑制Daxx表現時，顯著地調控655個基因的表達，進一步利用基因功能性分析，發現其中許多基因與細胞型態及癌症生成高度相關。此結果暗示Daxx可能參與癌症轉移的調控。另一方面，當抑制Daxx表現時，細胞內有104個長非編碼RNA表現量出現顯著差異。進一步利用生物資訊分析方法，篩選出Daxx可能調控的長非編碼RNA，我們並利用補救實驗及反轉錄定量聚合酶鏈式反應( RT-qPCR) 驗證該分析結果。結果證實12個長非編碼RNA受到Daxx調控，其中包含功能已知的lincRNA, 如JPX, NEAT1及MIAT。接著，我們利用RNA干擾技術發現其中一個長非編碼RNA，linc4971的表現對於其上游基因,ZNF703及ERLIN2具有抑制的作用。整體來說，本實驗結果除了提供Daxx 可能調控的標的基因及長非編碼RNA，並指出Daxx可藉由調控長非編碼RNA影響下游基因的表現。 | zh_TW |
| dc.description.abstract | The death domain-associated protein (Daxx) participates in various biological processes depending on its sub-cellular localization. In the nucleus, Daxx, as a transcriptional coregulator, interacts with various proteins, including transcription factors, to regulate gene expression. Although many Daxx-regulated genes have been reported, a genome-wide analysis of gene expression profile regulated by Daxx largely remains unclear. Here, we used microarray analysis to identify Daxx-regulated protein-coding genes as well as non-coding RNAs. 655 genes were significantly regulated in Daxx knockdown cells. Gene ontology analysis demonstrated that Daxx-regulated genes showed significant asssociation with cell morphology and cancer, suggesting that Daxx may play a role in tumor formation. Moreover, by combining microarray data and bioinformatic analysis, we identified 45 Daxx-regulated large intergenic non-coding RNAs (lincRNAs). Some identified lincRNAs, such as JPX, NEAT1 and MIAT, are functionally well-known, while most are recently defined transcripts. Notably, knockdown of identified lincRNA linc-4971 resulted in a activation of nearby gene expression, suggesting that this lincRNA may act as regulatory node in Daxx-mediated transcriptional pathways. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-17T09:18:41Z (GMT). No. of bitstreams: 1 ntu-101-R99448013-1.pdf: 1873252 bytes, checksum: a2b87f5f42d60a2d1ffc8542a7bdd314 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 中文摘要 1
English Abstract 2 Chapter I: Introduction 3 Daxx 4 LincRNAs 11 Specific aims 18 Chapter II: Materials and Methods 19 Cell culture and transfection 20 Plasmids and RNA interference 20 RT-quantitative PCR (RT-qPCR) 20 Microarray analysis 24 Chapter III Results 27 Transcriptional profile of knockdown of Daxx 28 The identification of Daxx-regulated lincRNAs 29 Evolutionary conservation of Daxx-mediated lincRNAs 30 Chromatin signature of Daxx-mediated lincRNAs 31 Tissue specificity of Daxx-mediated lincRNAs 31 Daxx-regulated lincRNAs affect gene expression in cis 32 Chapter IV: Discussion 34 Chapter V: Figures 41 Chapter VI: Tables 53 References 56 | |
| dc.language.iso | en | |
| dc.title | Daxx調控非編碼長RNA之鑑定及分析 | zh_TW |
| dc.title | Identification and analysis of Daxx-regulated large intergenic non-coding RNAs | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 阮麗蓉(Li-Jung Juan),徐立中(Li-Chung Hsu) | |
| dc.subject.keyword | Daxx,微陣列晶片分析,長非編碼RNA, | zh_TW |
| dc.subject.keyword | Daxx,large intergenic non-coding RNA,microarray, | en |
| dc.relation.page | 61 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2012-07-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf | 1.83 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。