Functional characterization of DNA methylation in Drosophila

果蝇 DNA 甲基化的功能表征

• 批准号: 5370376
• 负责人: Professor Dr. Frank Lyko
• 金额: --
• 依托单位: Abteilung Epigenetik
• 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/5370376?language=en
• 关键词: Functional; characterization; DNA; methylation; Drosophila

DNA methylation plays an important role in epigenetic gene regulation of higher eukaryotes like plants and mammals. Loss (or reduction) of methylation in these organisms results in dramatic but little understood developmental problems. We have shown recently that genomic DNA of the fruit fly Drosophila melanogaster is methylated specifically during early embryogenesis. The genome sequence of Drosophila contains a single candidate gene, dDnmt2, that has been predicted to encode a (cytosine-5) DNA methyltransferase. Dnmt2 genes are the most widely distributed eukaryotic DNA methyltransferase genes suggesting an important function in epigenetic gene regulation. For a detailed characterization of dDnmt2 we will thoroughly analyze the functional organization of the gene and then generate transgenic flies that carry either a targeted deletion of the gene or a transgene for inducible overexpression. A detailed molecular analysis of mutant flies will provide important results regading the role of dDnmt2 as well as the function of DNA methylation during Drosophila development. These experiments will be complemented by an analysis of subnuclear dDnmt2 distribution and genomic 5-methylcytosine during fly development. The experimental accessibility of the fly will generate a large wealth of data that will significantly deepen our understanding of epigenetic inheritance and establish Drosophila as a central model system for DNA methylation research.

DNA甲基化在高等真核生物如植物和哺乳动物的表观遗传基因调控中起着重要作用。甲基化的丧失（或减少）在这些生物体中导致戏剧性的，但很少了解的发育问题。我们最近已经表明，果蝇基因组DNA甲基化，特别是在早期胚胎发生。果蝇的基因组序列包含一个候选基因dDnmt 2，它被预测编码一个（胞嘧啶-5）DNA甲基转移酶。Dnmt 2基因是真核生物中分布最广的DNA甲基转移酶基因，在表观遗传基因调控中具有重要功能。对于dDnmt 2的详细表征，我们将彻底分析该基因的功能组织，然后产生携带基因的靶向缺失或用于诱导性过表达的转基因的转基因果蝇。对果蝇突变体的分子生物学分析将为研究dDnmt 2基因在果蝇发育中的作用以及DNA甲基化的功能提供重要的结果。这些实验将补充亚核dDnmt 2分布和基因组5-甲基胞嘧啶在苍蝇发育过程中的分析。果蝇的实验可及性将产生大量丰富的数据，这些数据将大大加深我们对表观遗传的理解，并将果蝇建立为DNA甲基化研究的中心模型系统。