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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余榮熾 | |
| dc.contributor.author | Yu-Hsin Kao | en |
| dc.contributor.author | 高幼昕 | zh_TW |
| dc.date.accessioned | 2021-06-17T03:22:52Z | - |
| dc.date.available | 2020-07-17 | |
| dc.date.copyright | 2018-07-17 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-06-15 | |
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Cartharius, K., et al., MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics, 2005. 21(13): p. 2933-42. 43. Latinkic, B.V., M. Zeremski, and L.F. Lau, Elk-1 can recruit SRF to form a ternary complex upon the serum response element. Nucleic Acids Res, 1996. 24(7): p. 1345-51. 44. Verduci, L., et al., microRNA-181a enhances cell proliferation in acute lymphoblastic leukemia by targeting EGR1. Leuk Res, 2015. 39(4): p. 479-85. 45. Shen, X., et al., MiR-424 regulates monocytic differentiation of human leukemia U937 cells by directly targeting CDX2. Biotechnol Lett, 2013. 35(11): p. 1799-806. 46. Cortes, M., et al., Control of lymphocyte development by the Ikaros gene family. Curr Opin Immunol, 1999. 11(2): p. 167-71. 47. Chen, P.Y., et al., Down-regulation of the oncogene PTTG1 via the KLF6 tumor suppressor during induction of myeloid differentiation. PLoS One, 2013. 8(8): p. e71282. 48. Morris, V.A., et al., Deregulated KLF4 Expression in Myeloid Leukemias Alters Cell Proliferation and Differentiation through MicroRNA and Gene Targets. Mol Cell Biol, 2016. 36(4): p. 559-73. 49. Lulli, V., et al., Overexpression of Ets-1 in human hematopoietic progenitor cells blocks erythroid and promotes megakaryocytic differentiation. Cell Death Differ, 2006. 13(7): p. 1064-74. 50. Dore, L.C. and J.D. Crispino, Transcription factor networks in erythroid cell and megakaryocyte development. Blood, 2011. 118(2): p. 231-9. 51. Ge, Y., et al., The role of the proto-oncogene ETS2 in acute megakaryocytic leukemia biology and therapy. Leukemia, 2008. 22(3): p. 521-9. 52. Horita, H., et al., Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation. Nat Commun, 2016. 7: p. 10830. 53. Huh, S., et al., Suppression of the ERK-SRF axis facilitates somatic cell reprogramming. Exp Mol Med, 2018. 50(2): p. e448. 54. Min, I.M., et al., The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell, 2008. 2(4): p. 380-91. 55. Lomberg, H. and C.S. Eden, Influence of P blood group phenotype on susceptibility to urinary tract infection. FEMS Microbiol Immunol, 1989. 1(6-7): p. 363-70. 56. Ziegler, T., N. Jacobsohn, and R. Funfstuck, Correlation between blood group phenotype and virulence properties of Escherichia coli in patients with chronic urinary tract infection. Int J Antimicrob Agents, 2004. 24 Suppl 1: p. S70-5 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69662 | - |
| dc.description.abstract | 人類的P1PK血型系統，主要包含在紅血球表面的P1及Pk醣類抗原，此兩種抗原的生成主要皆由醣轉移酶α4Gal-T負責。編碼α4Gal-T的A4GALT基因，其表現量高低與P1抗原的含量高低成正相關，因此為決定P1/P2表現型的關鍵基因。
單核苷酸多型性 (single nucleotide polymorphism, SNP) 是由單一核苷酸的不同形成DNA序列上的差異，影響同一物種之間基因組的多樣性。在我們實驗室過去的研究發現，位於A4GALT基因1號內含子的SNP rs5751348 (SNP 6)，能夠決定A4GALT基因表現量的高低，進而影響P1/P2表型的差異。SNP造成的單一核苷酸差異使得特定轉錄因子在該序列上有不同程度的結合能力。我們發現，轉錄因子EGR1能夠結合在SNP 6的P1基因型上，造成A4GALT基因型P1及P2的差異性表現。 同時，我們還觀察到在紅白血病 (erythroleukemia) 細胞株中，EGR1的基因表現量比起EGR家族的其他轉錄因子高出許多，且在K-562細胞中，加入sodium butyrate使K-562分化為紅血球細胞，EGR1的表現也大幅提升，因此我們想探討在紅血球細胞中，EGR1的基因調控機制。 我們利用報導基因分析法 (reporter assay) 檢驗EGR1基因組的5'端調控區域，篩選出EGR1可能的調控區域，進而使用電腦軟體TRANSFAC®、MatInspector及PROMO，預測該序列可能高度結合的轉錄因子，候選出與血球系統有關的轉錄因子：KLF4、KLF6、ETS1、ETS2、GATA1、GATA2、Ikaros及SRF，再將其大量表現於K-562細胞中，觀察EGR1的基因表現量是否因此大幅提高，並確認此基因調控機制，與血球細胞分化之間的關聯。 | zh_TW |
| dc.description.abstract | The antigens in the P1PK blood group system includes glycosphingolipids P1 and Pk. The A4GALT-encoded galactosyltransferase α4Gal-T synthesizes both P1 and Pk antigens. The quantity of A4GALT expression has been shown to be positively correlated with the amount of P1 antigens and quantitative difference of P1 antigen expression corresponds to P1/P2 phenotype.
Single nucleotide polymorphism (SNP) is a variation of single nucleotide that occurs at a specific position in the genome and the variation results in the polymorphic diversity within a population. Based on the previous studies in our lab, SNP 6, which locates on the intron 1 of A4GALT, has been demonstrated to correlate with the expression levels of A4GALT and consequently determines the P1/P2 phenotype. SNP in the regulatory region of a gene may affect the binding ability of a specific transcription factor on the located sequences. Our results revealed that the transcription factor EGR1 differentially binds to the SNP6 region with the different genotypes. The expression profiles of the EGR transcription factor family, EGR1~EGR4, were analyzed in the various erythroid-lineage cells. The results showed that EGR1 had higher expression level than the other EGR family members, EGR2-EGR4. Moreover, after treated with sodium butyrate to induce K-562 cells to differentiate into erythrocytic cells, the gene expression of EGR1 increased significantly. This evoked our curiosity about how EGR1 was regulated during erythroid differentiation. In this research, we aimed to elucidate the molecular details of the transcriptional regulation of EGR1 during erythroid differentiation. The 5’-region of EGR1 gene were analyzed by reporter assay and determined the region that showed higher transcriptional activity. The potential transcription factor binding motifs in the region were predicted using online databases, KLF4, KLF6, ETS1, ETS2, GATA1, GATA2, Ikaros and SRF were implicated to be the candidate transcription factors responsible for transcription activation. These candidate transcription factors had been reported to be associated with hematopoietic system. In the present study, these transcription factors were ectopically expressed in K-562 cells in order to analyze their ability to induce the transcriptional level of EGR1. However, none of these transcription factors showed the ability to induce the transcriptional activity of the specific 5’-region of EGR1. Further studies are needed to elucidate the regulatory mechanism for the EGR1 expression during erythroid differentiation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T03:22:52Z (GMT). No. of bitstreams: 1 ntu-107-R05b46020-1.pdf: 2010283 bytes, checksum: e2337e4dca0b31f2cc8d32c2a6e1928e (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
中文摘要 ii 英文摘要 iii 縮寫表 v 目錄 vii 圖目錄 ix 第一章 緒論 1 1.1 人類P1PK血型系統 1 1.2 α-1,4-Galactosyltransferase (α4Gal-T) 2 1.3 A4GALT基因表現之調控與P1/P2血型之關聯 2 1.4 Early Growth Response 1 (EGR1) 3 1.5 研究構想與目的 4 第二章 實驗材料與方法 5 2.1 細胞培養與分化 (Cell Culture) 5 2.2 RNA表現之分析 5 2.2.1 RNA萃取 5 2.2.2 反轉錄聚合酶連鎖反應 (Reverse Transcription Polymerase Chain Reaction) 5 2.2.3 即時定量聚合酶連鎖反應 (Real-Time Polymerase Chain Reaction) 5 2.3 報導基因分析法 (Reporter Assay) 6 2.4 基因轉殖－脂質體轉染法 (Liposome Tranfection) 7 2.5 蛋白質表現系統與西方墨點法 (Western Blot) 7 第三章 結果 9 3.1轉錄因子EGR1在類紅血球細胞分化前後的表現差異 9 3.2 EGR1基因調控位置 9 3.2.1 ENCODE資料庫分析EGR1基因高轉錄活性區域 9 3.2.2 縮小EGR1基因調控區域的範圍 10 3.3不同轉錄因子對EGR1基因轉錄活性之影響 11 3.3.1 利用軟體預測及分析可能會和EGR1基因調控區域結合之轉錄因子 11 3.3.2 分析可能有結合能力的轉錄因子對EGR1基因之轉錄活性的影響 12 第四章 討論 14 第五章 圖表 17 參考文獻 25 附錄 29 | |
| dc.language.iso | zh-TW | |
| dc.subject | K-562 | zh_TW |
| dc.subject | 紅血球分化 | zh_TW |
| dc.subject | 轉錄因子EGR1 | zh_TW |
| dc.subject | K-562 | en |
| dc.subject | erythroid differentiation | en |
| dc.subject | transcription factor EGR1 | en |
| dc.title | 轉錄因子EGR1在紅血球分化過程中的基因調控機制 | zh_TW |
| dc.title | Regulation of EGR1 Gene Expression in Erythroid Differentiation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 朱善德,涂玉青 | |
| dc.subject.keyword | 轉錄因子EGR1,K-562,紅血球分化, | zh_TW |
| dc.subject.keyword | transcription factor EGR1,K-562,erythroid differentiation, | en |
| dc.relation.page | 32 | |
| dc.identifier.doi | 10.6342/NTU201800960 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-06-15 | |
| 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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