Gene Expression in the Preimplantation Mouse Embryo

植入前小鼠胚胎中的基因表达

基本信息

  • 批准号:
    8105487
  • 负责人:
  • 金额:
    $ 36.89万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1987
  • 资助国家:
    美国
  • 起止时间:
    1987-09-01 至 2013-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this application is to determine underlying mechanisms that govern changes in gene expression during oocyte growth and the maternal-to-zygotic transition, both of which are linked and essential for development. A universal feature of oocyte development is that transcription declines commencing around mid-growth such that fully-grown oocytes are essentially transcriptionally quiescent. In mouse, this decline correlates with visible changes in chromatin structure, which becomes more condensed and decreased activity of the transcription machinery. Using a transgenic RNAi approach that permits study of the function of any gene in oocyte development, Specific Aim 1 will test the hypothesis that members of the HP1 family of chromatin-binding proteins and UBC9, via its central role in sumoylation, are essential for changes in chromatin structure and transcriptional activity that occur during oocyte growth. A major reprogramming of gene expression is first detected during the 2-cell stage and essential for continued development. Superimposed on genome activation is development of a chromatin-mediated transcriptionally repressive state. Our transcript profiling experiments identified Myc as a candidate gene pivotal for genome activation and reprogramming of gene expression, and Hdad as essential for establishing the transcriptionally repressive state. Using an RNAi approach to target Myc and Hdad, Specific Aim 2 will test the hypothesis that Myc and Hdad are critical for these two processes that collaboratively sculpt the appropriate pattern of gene expression required for successful development following genome activation. Oocytes express miRNAs and mRNA degradation, which initiates during oocyte maturation and continues during early preimplantation development, is a post-transcriptional mechanism that contributes to determining the global pattern of gene expression in the embryo. Specific Aim 3 will test the hypothesis that miRNAs target specific mRNAs for degradation in P-bodies and that this mechanism is essential for proper oocyte/embryo development. The proposed studies will increase our basic knowledge and understanding of human development. In the near term, they may help improve treatment of human infertility by providing new knowledge that will facilitate the rational development of treatments that foster improved oocyte and preimplantation embryo development in the practice of Assisted Reproductive Technology (ART).
描述(申请人提供):本申请的长期目标是确定控制卵母细胞生长和母体向合子转变过程中基因表达变化的潜在机制,这两个过程都是联系在一起的,对发育至关重要。卵母细胞发育的一个普遍特征是,转录从中期开始下降,因此完全发育的卵母细胞基本上处于转录静止状态。在小鼠中,这种下降与染色质结构的明显变化有关,染色质结构变得更加浓缩,转录机制的活性降低。利用转基因RNAi方法,可以研究任何基因在卵母细胞发育中的功能,特殊目的1将检验这一假设,即染色质结合蛋白HP1家族的成员和UBC9,通过其在总酰化中的中心作用,对于卵母细胞生长过程中发生的染色质结构和转录活性的变化是必不可少的。基因表达的重大重新编程首先在2-细胞阶段被检测到,并且对于继续发育是必不可少的。叠加在基因组激活上的是染色质介导的转录抑制状态的发展。我们的转录图谱实验确定Myc是基因组激活和基因表达重新编程的关键候选基因,而Hda是建立转录抑制状态所必需的。使用RNAi方法针对Myc和Hda,特定的目标2将检验这样的假设,即Myc和Hda对这两个过程至关重要,这两个过程协同塑造了基因组激活后成功发育所需的适当的基因表达模式。卵母细胞表达miRNAs和mRNA降解,开始于卵母细胞成熟并持续到着床前发育早期,是一种转录后机制,有助于决定胚胎中基因表达的整体模式。具体目标3将测试假设,即miRNAs针对P小体中的特定mRNAs进行降解,并且这一机制对于正常的卵母细胞/胚胎发育是必不可少的。拟议的研究将增加我们对人类发展的基本知识和理解。在短期内,它们可能会通过提供新的知识来帮助改善人类不孕不育的治疗,这将促进在辅助生殖技术(ART)实践中促进改善卵母细胞和植入前胚胎发育的治疗方法的合理发展。

项目成果

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RICHARD M SCHULTZ其他文献

RICHARD M SCHULTZ的其他文献

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{{ truncateString('RICHARD M SCHULTZ', 18)}}的其他基金

Gene Expression in the Preimplantation Mouse Embryo
植入前小鼠胚胎中的基因表达
  • 批准号:
    8135897
  • 财政年份:
    2010
  • 资助金额:
    $ 36.89万
  • 项目类别:
Basonuclin and Ribosome Biogenesis in Mouse Oocyte and Embryo
小鼠卵母细胞和胚胎中的基底核蛋白和核糖体生物发生
  • 批准号:
    7760658
  • 财政年份:
    2009
  • 资助金额:
    $ 36.89万
  • 项目类别:
Gene Expression in the Preimplantation Mouse Embryo
植入前小鼠胚胎中的基因表达
  • 批准号:
    7936524
  • 财政年份:
    2009
  • 资助金额:
    $ 36.89万
  • 项目类别:
Basonuclin and Ribosome Biogenesis in Mouse Oocyte and Embryo
小鼠卵母细胞和胚胎中的基底核蛋白和核糖体生物发生
  • 批准号:
    7587729
  • 财政年份:
    2009
  • 资助金额:
    $ 36.89万
  • 项目类别:
Impact of Egg Quality on Gene Expression and Behavior
卵子质量对基因表达和行为的影响
  • 批准号:
    6671981
  • 财政年份:
    2003
  • 资助金额:
    $ 36.89万
  • 项目类别:
Impact of Egg Quality on Gene Expression and Behavior
卵子质量对基因表达和行为的影响
  • 批准号:
    6787309
  • 财政年份:
    2003
  • 资助金额:
    $ 36.89万
  • 项目类别:
Impact of Egg Quality on Gene Expression and Behavior
卵子质量对基因表达和行为的影响
  • 批准号:
    6941214
  • 财政年份:
    2003
  • 资助金额:
    $ 36.89万
  • 项目类别:
Impact of Egg Quality on Gene Expression and Behavior
卵子质量对基因表达和行为的影响
  • 批准号:
    7109360
  • 财政年份:
    2003
  • 资助金额:
    $ 36.89万
  • 项目类别:
Impact of Egg Quality on Gene Expression and Behavior
卵子质量对基因表达和行为的影响
  • 批准号:
    7282057
  • 财政年份:
    2003
  • 资助金额:
    $ 36.89万
  • 项目类别:
Epigenetic Regulation of Imprinting in Mouse Embryo
小鼠胚胎印记的表观遗传调控
  • 批准号:
    6622856
  • 财政年份:
    2002
  • 资助金额:
    $ 36.89万
  • 项目类别:

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