Epigenetic control of retrotransposon silencing in somatic cells of Drosohpila by the cytosine 5 Methyltransferase DNMT2

胞嘧啶5甲基转移酶DNMT2对果蝇体细胞逆转录转座子沉默的表观遗传控制

• 批准号: 119070512
• 负责人: Professor Dr. Gunter Reuter (†)
• 金额: --
• 依托单位: Abteilung Entwicklungsgenetik
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/119070512?language=en
• 关键词: Epigenetic; control; retrotransposon; silencing; somatic

The central aim of our studies consists in resolving the epigenetic function of DNMT2 in the Drosophila model system. DNMT2 is involved in retrotransposon and repeatdependent gene silencing monitored by variegated expression of the white reporter gene. Histone methyltransferases involved in these silencing processes are SUV4-20 and SETDB1 and functional interdependence of DNMT2 with these enzymes in recognition, binding and epigenetic indexing at specific target site will be studied. First Dnmt2 point mutations were isolated and systematic genetic dissection of DNMT2 function in these processes will be performed. Dnmt2 is very early zygotically expressed and its epigenetic indexing in early embryogenesis is studied by ChIP analysis. Dnmt2 expression levels strongly depend on the genetic background. For identification of factors controlling Dnmt2 expression wild type populations will be assayed using transgenic expression reporter systems for genetic analysis. Beside analysis of the role of retrotransposons in control of DNMT2 dependent silencing processes the epigenetic function of a series of newly identified modifiers of these processes will be molecularly analysed. It will be studied whether a putative TET1 homolog of Drosophila functions in demethylation of 5-mC.

我们研究的中心目标在于解决果蝇模型系统中 DNMT2 的表观遗传功能。 DNMT2 参与逆转录转座子和通过白色报告基因的多样化表达监测的重复依赖性基因沉默。参与这些沉默过程的组蛋白甲基转移酶是 SUV4-20 和 SETDB1，将研究 DNMT2 与这些酶在特定靶位点的识别、结合和表观遗传索引中的功能相互依赖性。首先分离出 Dnmt2 点突变，并对这些过程中 DNMT2 功能进行系统的遗传解剖。 Dnmt2 非常早期合子表达，通过 ChIP 分析研究其在早期胚胎发生中的表观遗传索引。 Dnmt2 表达水平很大程度上取决于遗传背景。为了鉴定控制 Dnmt2 表达的因素，将使用转基因表达报告系统对野生型群体进行遗传分析。除了分析反转录转座子在控制 DNMT2 依赖性沉默过程中的作用之外，还将对这些过程的一系列新鉴定的修饰因子的表观遗传功能进行分子分析。将研究果蝇推定的 TET1 同源物是否在 5-mC 去甲基化中发挥作用。