WEKO3
アイテム
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This property is maintained during early preimplantation development, but is lost around the late-preimplantation stage. The mechanism underlying acquisition and maintenance of the totipotent state remains largely unknown. Oocytes express the genes in their specific pattern during oogenesis. This pattern is drastically altered into zygote-specific one after fertilization and thereafter it is dynamically changed during preimplantation development. In general, gene expression is epigenetically regulated. When cells are divided, some epigenetic modifications are inherited from parental cells into daughter ones to maintain the gene expression pattern. This mechanism is called as \"cell memory\" and the epigenetic modifications inherited into the daughter cells are referred to as cell memory markers. As gene expression pattern is dynamically changed after fertilization, cell memory seems to be detrimental mechanisms for early preimplantation embryos to acquire and maintenance of totipotency. Therefore, I hypothesized that cell memory mechanisms might not function after fertilization. In this thesis, to understand the mechanism regulating the acquisition and maintenance of totipotency in the early preimplantation embryos, I examined the dynamic changes of Histone H3 Lysine 79 dimethylation (H3K79me2), a cell memory marker of the active genes, during oogenesis and preimplantation development, and then investigated the mechanisms that regulate H3K79me2 during 1- and 2-cell stages. In Chapter 1, I show that H3K79me2 was present during oocytes growth and maturation. However, it was eliminated just after fertilization and the H3K79 hypomethylation state was sustained until 4-cell stage. At the blastocyst stage H3K79me2 increased. Therefore, it was possible that elimination of H3K79me2 plays a role in acquisition of totipotency. To investigate the involvement of H3K79me2 elimination in acquisition of totipotency, I examined H3K79me2 in the somatic nuclei transplanted into enucleated unfertilized oocytes in which totipotency is acquired. H3K79me2 was eliminated in the transplanted somatic nuclei soon after parthenogenetic activation. In contrast, the elimination of H3K79me2 did not occur in the nuclei transplanted into the parthenogenetically activated embryos in which totipotency is not acquired. These results suggest that the erasing of H3K79me2 is involved in the acquisition of totipotency after fertilization. In chapter 2, I examined the dynamics of Dot1L (Disruptor of telomeric silencing 1 like) which is thought to be sole H3K79 methyltransferase to understand the mechanisms for maintenance of H3K79 hypomethylation state during 1- and 2-cell stages. At 1-cell stage, Dot1L was localized in the pronuclei. 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Involvement of Histone H3 lysine 79 methylation and Dot1L in the mechanism regulating totipotency in mouse preimplantation embryos
https://doi.org/10.15083/00005595
https://doi.org/10.15083/00005595f69bf86a-0488-4d69-b610-164f4a84c653
名前 / ファイル | ライセンス | アクション |
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K-03548.pdf (12.2 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2014-02-24 | |||||
タイトル | ||||||
タイトル | Involvement of Histone H3 lysine 79 methylation and Dot1L in the mechanism regulating totipotency in mouse preimplantation embryos | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | Totipotency | |||||
主題Scheme | Other | |||||
キーワード | ||||||
主題 | Histone H3 lysine 79 methylation | |||||
主題Scheme | Other | |||||
キーワード | ||||||
主題 | Dot1L | |||||
主題Scheme | Other | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_46ec | |||||
タイプ | thesis | |||||
ID登録 | ||||||
ID登録 | 10.15083/00005595 | |||||
ID登録タイプ | JaLC | |||||
その他のタイトル | ||||||
その他のタイトル | マウス着床前初期発生における分化全能性調節へのHistone H3 lysine 79 メチル化およびDot1Lの関与 | |||||
著者 |
Ooga, Masatoshi
× Ooga, Masatoshi |
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著者別名 | ||||||
識別子 | 11666 | |||||
識別子Scheme | WEKO | |||||
姓名 | 大我, 政敏 | |||||
著者所属 | ||||||
著者所属 | 東京大学大学院新領域創成科学研究科生命科学研究系先端生命科学専攻 | |||||
著者所属 | ||||||
著者所属 | Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo | |||||
Abstract | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | After fertilization terminally differentiated oocytes acquire totipotency. This property is maintained during early preimplantation development, but is lost around the late-preimplantation stage. The mechanism underlying acquisition and maintenance of the totipotent state remains largely unknown. Oocytes express the genes in their specific pattern during oogenesis. This pattern is drastically altered into zygote-specific one after fertilization and thereafter it is dynamically changed during preimplantation development. In general, gene expression is epigenetically regulated. When cells are divided, some epigenetic modifications are inherited from parental cells into daughter ones to maintain the gene expression pattern. This mechanism is called as "cell memory" and the epigenetic modifications inherited into the daughter cells are referred to as cell memory markers. As gene expression pattern is dynamically changed after fertilization, cell memory seems to be detrimental mechanisms for early preimplantation embryos to acquire and maintenance of totipotency. Therefore, I hypothesized that cell memory mechanisms might not function after fertilization. In this thesis, to understand the mechanism regulating the acquisition and maintenance of totipotency in the early preimplantation embryos, I examined the dynamic changes of Histone H3 Lysine 79 dimethylation (H3K79me2), a cell memory marker of the active genes, during oogenesis and preimplantation development, and then investigated the mechanisms that regulate H3K79me2 during 1- and 2-cell stages. In Chapter 1, I show that H3K79me2 was present during oocytes growth and maturation. However, it was eliminated just after fertilization and the H3K79 hypomethylation state was sustained until 4-cell stage. At the blastocyst stage H3K79me2 increased. Therefore, it was possible that elimination of H3K79me2 plays a role in acquisition of totipotency. To investigate the involvement of H3K79me2 elimination in acquisition of totipotency, I examined H3K79me2 in the somatic nuclei transplanted into enucleated unfertilized oocytes in which totipotency is acquired. H3K79me2 was eliminated in the transplanted somatic nuclei soon after parthenogenetic activation. In contrast, the elimination of H3K79me2 did not occur in the nuclei transplanted into the parthenogenetically activated embryos in which totipotency is not acquired. These results suggest that the erasing of H3K79me2 is involved in the acquisition of totipotency after fertilization. In chapter 2, I examined the dynamics of Dot1L (Disruptor of telomeric silencing 1 like) which is thought to be sole H3K79 methyltransferase to understand the mechanisms for maintenance of H3K79 hypomethylation state during 1- and 2-cell stages. At 1-cell stage, Dot1L was localized in the pronuclei. However ubiquitinated histone H2B (ubH2B), which is required for Dot1L-mediated H3K79 methylation, was at a low level. On the other hand, at 2-cell stage, although ubH2B was detected at a high level, Dot1L was exported from the nuclei by the mechanism involving its nuclear export domain 1 (NED1) and 2 (NED2). Thus, the absence of H3K79me2 is maintained by different mechanisms during 1- and 2-cell stages. A Dot1L deletion mutant that lacks NED1 and NED2 (referred to as N393-NLS1) is localized in nuclei at 2-cell stage. Expression of N393-NLS1 caused methylation of H3K79 and developmental arrest at 2-cell stage. These results suggest that 2-cell stage-specific nuclear export of Dot1L is important for the maintenance of H3K79 hypomethylation and the progression of preimplantation development. In conclusion, H3K79me2 was eliminated after fertilization and sustained at a low level during 1- and 2-cell stage. These results suggest that totipotency is acquired by elimination of H3K79me2 and maintained by the absence of H3K79me2. | |||||
書誌情報 | 発行日 2012-03-22 | |||||
日本十進分類法 | ||||||
主題 | 481 | |||||
主題Scheme | NDC | |||||
学位名 | ||||||
学位名 | 博士(生命科学) | |||||
学位 | ||||||
値 | doctoral | |||||
学位分野 | ||||||
Integrated Biosciences (生命科学) | ||||||
学位授与機関 | ||||||
学位授与機関名 | University of Tokyo (東京大学) | |||||
研究科・専攻 | ||||||
Department of Integrated Biosciences, Graduate School of Frontier Sciences (新領域創成科学研究科先端生命科学専攻) | ||||||
学位授与年月日 | ||||||
学位授与年月日 | 2012-03-22 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲第28408号 | |||||
学位記番号 | ||||||
博創域第767号 |