Parent-specific methylation reprogramming in early embryos: implications for mammalian development and embryo biotechnology

早期胚胎中亲本特异性甲基化重编程：对哺乳动物发育和胚胎生物技术的影响

• 批准号: 5370148
• 负责人: Professor Dr. Thomas Haaf
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5370148?language=en
• 关键词: Parent; specific; methylation; reprogramming; early

Our aim is a better understanding of the functional significance of genome-wide opposing patterns in paternal and maternal DNA methylation during preimplantation development. We will analyze the evolutionary conservation of differential demethylation of the paternal and maternal genomes in representative mammalian (mouse, cattle, pig, rabbit) and lower vertebrate species (medaka, zebrafish) as well as the frequency and consequences of disturbed methylation reprogramming in mouse embryos from normal matings and in vitro production. Our experiments will show whether abnormal methylation patterns in mammalian embryos contribute to the high incidence of early pregnancy failure. Since methylation reprogramming defects may also have important implications for mammalian cloning, we will analyze the methylation patterns in cloned rabbit embryos, using different nuclear transfer protocols and embryo culture systems. In addition, we will study the higher-order nuclear organization of imprinted gene clusters, which are protected from genome-wide demethylation during preimplantation development. We assume that a specific functional architecture of the early embryonic nucleus is important for genomic imprinting and methylation reprogramming.

我们的目的是更好地了解在植入前发育过程中父方和母方DNA甲基化的全基因组相反模式的功能意义。我们将分析代表性哺乳动物（小鼠，牛，猪，兔）和低等脊椎动物物种（青鳉，斑马鱼）的父系和母系基因组的差异去甲基化的进化保守性，以及正常交配和体外生产的小鼠胚胎中干扰甲基化重编程的频率和后果。我们的实验将显示哺乳动物胚胎中的异常甲基化模式是否有助于早期妊娠失败的高发病率。由于甲基化重编程缺陷也可能对哺乳动物克隆产生重要影响，因此我们将使用不同的核移植方案和胚胎培养系统分析克隆兔胚胎中的甲基化模式。此外，我们将研究印迹基因簇的高级核组织，这些基因簇在植入前发育过程中受到全基因组去甲基化的保护。我们假设早期胚胎细胞核的特定功能结构对于基因组印记和甲基化重编程是重要的。