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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張智芬(Zee-Fen Chang) | |
| dc.contributor.author | Pi-Chiang Hsu | en |
| dc.contributor.author | 許弼強 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:46:42Z | - |
| dc.date.available | 2006-08-04 | |
| dc.date.copyright | 2006-08-04 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33548 | - |
| dc.description.abstract | Rho-associated kinase (ROCK)調控的細胞膜皺縮在PMA誘發D2細胞凋亡過程中扮演了決定性的角色，該群細胞有細胞核結構改變、核染色質(chromatin)濃縮和RNA合成減少的現象。藉由冷光酵素活性系統(luciferase reporter system)分析第一、二和三型聚合脢所從屬的基因表現，我發現第一、二和三型聚合脢所從屬的基因表現皆會被ROCK(CAT)抑制，說明ROCK的過度活化足以抑制普遍性的基因轉錄。由於ROCK造成的細胞皺縮不會使核染色質過度包裹到無法被微球菌核酸脢(micrococcal nuclease)切割的狀態，顯示ROCK所造成轉錄的抑制不是導因於核染色質更高度秩序(higher-order)的濃縮。藉由分析組蛋白的修飾得知在HEK 293T細胞中ROCK(CAT)的表現會造成組蛋白H3的K9三甲基化增加及S10磷酸化減少，而不影響組蛋白H2B的S14磷酸化。我同時利用核染色質免疫沈澱法(ChIP)證實在表現ROCK(CAT)的HEK 293T以及處理PMA的D2細胞中，位於rRNA啟動子區域的組蛋白H3有K9三甲基化增加的現象。已知在核染色質重組所造成的轉錄抑制機轉中，組蛋白H3的K9甲基化扮演一關鍵性的角色，因此我認為透過活化ROCK所造成的細胞皺縮可能傳遞一個促進組蛋白H3 K9甲基化的訊息。有趣的是，利用siRNA降低組蛋白甲基轉移脢G9a的表現可以減緩ROCK(CAT)所造成的轉錄抑制以及組蛋白H3 K9三甲基化增加。因此我推論細胞質中ROCK所引發的皺縮訊息可傳遞到細胞核，透過G9a的作用促進核染色質重組導致基因轉錄的抑制。 | zh_TW |
| dc.description.abstract | In phorbol ester-induced pro-apoptotic D2 cells, the Rho-associated kinase (ROCK) plays a determining role in membrane contraction, which concomitantly results in nuclear shape change, chromatin condensation and transcription repression. Using various luciferase reporter systems, I found that pol I, II and III-dependent transcriptions are all suppressed by ectopic expression of dominant active form of ROCK(CAT), indicating that too much ROCK activation is sufficient to shut-off general transcription. Here, I showed that ROCK-mediated contraction does not make chromatin too packed to be accessed by micrococcal nuclease digestion, indicating that ROCK-mediated transcription repression is not a result of a higher-order chromatin condensation. By analyzing histone modifications, I found that expression of ROCK(CAT) in HEK 293T cells increased K9 tri-methylation of histone H3 with decreased extent of S10 phosphorylation of histone H3, while S14 phosphorylation of histone H2B remained unaffected. Consistently, results from ChIP assays showed that K9-methylation of H3 in the rRNA promoter region was increased in both HEK 293T expressing ROCK(CAT) and PMA-induced pro-apoptotic D2 cells. Since it is well known that K9 methylation of H3 plays a crucial role in chromatin remodeling for transcriptional repression, it is very likely that ROCK-mediated contraction is capable of conferring signals for K9 methylation of H3 in nuclei. Of interest, depleted expression of G9a, a histone methyltransferase, restored transcription capacity in cells expressing ROCK(CAT) with a concurrent reduction in extent of K9 methylation of histone H3. Accordingly, I hypothesized that ROCK-mediated contraction in cytoplasm transmits signal to nucleus, where function of G9a is upregulated to remodel chromatin for transcriptional repression. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:46:42Z (GMT). No. of bitstreams: 1 ntu-95-R93442007-1.pdf: 710009 bytes, checksum: 0286b197ebd9ab36d8d74764519401ea (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………2
Abstract………………………………………………………...3 Introduction…………………………………………………….4 Materials and Methods………………………………………..14 Results…………………………………………………………25 Discussion……………………………………………………..33 Figures and Legends…………………………………………..37 References……………………………………………………..55 | |
| dc.language.iso | en | |
| dc.subject | 基因轉錄 | zh_TW |
| dc.subject | transcription | en |
| dc.subject | ROCK | en |
| dc.title | ROCK 抑制普遍性基因轉錄之探討 | zh_TW |
| dc.title | ROCK-dependent repression of general transcription | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳瑞華(Ruey-Hwa Chen),施修明,羅?升 | |
| dc.subject.keyword | 基因轉錄, | zh_TW |
| dc.subject.keyword | ROCK,transcription, | en |
| dc.relation.page | 61 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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