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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林劭品(Shau-Ping Lin) | |
dc.contributor.author | Yu-Han Yeh | en |
dc.contributor.author | 葉俞函 | zh_TW |
dc.date.accessioned | 2021-06-17T07:16:18Z | - |
dc.date.available | 2024-07-18 | |
dc.date.copyright | 2019-07-18 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-07-12 | |
dc.identifier.citation | Aapola, U., Kawasaki, K., Scott, H. S., Ollila, J., Vihinen, M., Heino, M., Shintani, A., Kawasaki, K., Minoshima, S., Krohn, K., Antonarakis, S. E., Shimizu, N., Kudoh, J., Peterson, P., 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, 293-8, doi:10.1006/geno.2000.6168.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73072 | - |
dc.description.abstract | 適當的生精作用是維持長期生育能力及後代健康的關鍵。類 3 號 DNA 甲 基化酶 (DNA methyltransferase 3-like, DNMT3L) 的缺乏將使生精作用停止並無法 抑制轉位子的跳躍,最終導致雄性不育。 DNMT3L 是表觀遺傳調節分子,其最 為人知的功能是在胚胎時期之雄性生殖細胞發育中促進 DNA 甲基化之重建。而 小鼠出生後的 DNMT3L 表現與否及其功能皆鮮少被描述。在此研究中,我們發 現全新的 DNMT3L 異構物,因其大量表現於成年小鼠睪丸中經減數分裂後之生 殖細胞,故取名為 DNMT3L-at (at: adult testes)。原本的 DMNT3L 是主要表現在 胚幹細胞,具有典型表觀遺傳調節功能,現在稱作 DNMT3L-s (s: stem cells)。 DNMT3L-at 主要位於細胞質,這與 DNMT3L-s 位於細胞核的特性大不相同。我 們從多種轉錄體與表觀基因體定序結果中推論 Dnmt3l-at 的啟動子於不同分化時 期之雄性生殖細胞有不同活躍程度。此外,DNMT3L-at 之蛋白表現量與細胞座落 位置從不同時期之免疫組織化學染色與分離核質蛋白之西方墨點法獲得確認。從 蛋白座落共同位置等實驗中得知 DNMT3L 與 PLZF 及 piRNA 調控路徑元件蛋 白之交互作用。暗示著 DNMT3L-at 具有非典型性功能。DNMT3L-at 之確切功能 研究與在減數分裂中扮演的角色還需要更精緻與精準之小鼠實驗模式來探討。 | zh_TW |
dc.description.abstract | Proper spermatogenesis is critical to maintain the long-term male fertility and the health status of offspring. DNA methyltransferase 3-like (DNMT3L) mutation leads to spermatogenesis arrest and failure to repress transposons elements (TE), eventually cause male infertility. DNMT3L is an epigenetic modulator well known for facilitating DNA methylation during embryonic male germ cell development. The expression and function of postnatal DNMT3L are scarcely described. In this study, I identified a novel isoform, DNMT3L-at (“at” refers to adult testis), highly enriched in post-meiotic germ cells. I also demonstrated its surprising cytoplasmic localization, in contrast to the known epigenomic modulation property for canonical DNMT3L-s (“s” refers to stem cells). I deduced Dnmt3l-at promoter and transcriptional activity from various omics profiles of different male germ cell developmental stages. In addition, I clarified the DNMT3L-at postnatal expression and cytoplasmic localization by immunohistochemistry (IHC) of seminiferous tubules from different ages, and Western bolt from cytoplasm and nucleus fractioned protein samples. Furthermore, combination of various protein co-localization analysis results, I discovered possible interaction between DNMT3L-PLZF, and PLZF-piRNA pathway components. These data implied a novel function of DNMT3L-at beyond epigenetic regulation. Functional mutagenesis is being designed to precisely eliminate DNMT3L-at without interfering DNMT3L-s, in order to test the significance of DNMT3L-at in regulating meiosis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:16:18Z (GMT). No. of bitstreams: 1 ntu-108-R06642003-1.pdf: 4695413 bytes, checksum: d3a116088e1b344598e167c209c9eccc (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 誌謝 (i)
中文摘要 (ii) ABSTRACT (iii) CONTENTS (v) LIST OF FIGURES (vii) LIST OF TABLES (ix) ABBREVIATIONS (x) Chapter 1 Introduction 1.1 Hazards in fertility (1) 1.2 Male germ cell development and spermatogenesis (2) 1.3 Spermatogonial stem cells (SSCs) for germ cell pool maintenance (4) 1.4 DNMT3L (DNA methyltransferase 3-like) play roles in retrotransposon repression and germ line maintenance (5) 1.5 PLZF a transcriptional factor involves in stem cell self-renewal and inhibits translation of TEs (8) 1.6 Post-transcriptional level of TEs silencing - piRNA pathway (9) 1.7 Significance (11) 1.8 Specific aims (12) Chapter 2 Materials and methods 2.1 Breeding of Dnmt3l mutant mouse (13) 2.2 Dnmt3l Genotyping (13) 2.3 X-gal Staining (15) 2.4 Immunohistochemistry (16) 2.5 Preparation of germ cell enriched single cell suspension (18) 2.6 THY1 Sorting and Subcellular Fractionation (19) 2.7 Western Blotting (21) 2.8 Immunocytochemistry (24) 2.9 Duolink® in situ PLA (proximity ligation assay) (25) Chapter 3 Results 3.1 Dnmt3l promoter activity in adult male germ cells (27) 3.2 Alternative Dnmt3l transcripts in PS and RS cell types (28) 3.3 DNMT3L expression in undifferentiated spermatogonia, spermatocytes, and spermatids (31) 3.4 Evaluating subcellular localization of various DNMT3L isoforms in different stages of spermatogenesis (33) 3.5 Co-localization of DNMT3L, PLZF and piRNA components in cytoplasm (35) Chapter 4 Discussion 4.1 Postnatal DNMT3L isoform expressions in male germ cells (37) 4.2 DNMT3L subcellular localization (39) 4.3 The potential DNMT3L-at function in piRNA regulation (40) 4.4 Perspective (41) 4.5 Conclusion (42) Reference (59) | |
dc.language.iso | en | |
dc.title | 小鼠雄性生殖細胞中類 3 號 DNA 甲基酶之新發現異構體與非典型功能探討 | zh_TW |
dc.title | Beyond Epigenetic Regulation: Non-Canonical Function and novel isoform of DNA Methyltransferase 3-Like in postnatal male germ cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳銘正(Ming-Cheng Chen),宋麗英(Li-Ying Sung),靖永皓(Yung-Hao Ching),黃彥華(Yen-Hua Huang) | |
dc.subject.keyword | 生殖細胞,生精作用,類 3 號 DNA 甲基化?異構物, | zh_TW |
dc.subject.keyword | Germ cell,Spermatogenesis,DNMT3L isoforms, | en |
dc.relation.page | 64 | |
dc.identifier.doi | 10.6342/NTU201901406 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-07-14 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
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