Analysis of the dynamics of epigenetic modifications during Drosophila germ line development

果蝇种系发育过程中表观遗传修饰的动态分析

• 批准号: 19022910
• 负责人: Professor Dr. Matthias Schaefer
• 金额: --
• 依托单位: Abteilung für Zell- und Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/19022910?language=en
• 关键词: Analysis; dynamics; epigenetic; modifications; during

Germ cells maintain life through the transmission of genetic information into the next generation. Germ cells have the potential to develop into any tissue, making it critical that they are protected from inappropriate differentiation. The mechanisms that provide this protection are unknown and are likely to be relevant to understanding how somatic stem cells maintain pluripotency. DNA-methylation and histone modifications play a major role in the epigenetic regulation of gene expression. We will analyze the function of these modifications during the segregation of the germ cell lineage from somatic cells, their transcriptional quiescence and the maintenance of their identity during embryonic development of Drosophila melanogaster. The host laboratory has established that Dnmt2 is responsible for the DNA-methylation of the fly genome and that high levels of Dnmt2-mediated methylation exist in pole cells (primordial germ cells). We will now globally analyse the dynamics of DNA-methylation and other epigenetic marks (covalent histone modifications) in developing germ Schaefer cells of both wildtype embryos and embryos mutant for genes involved in establishing and maintaining pole cell identity. This will be complemented by a genomic profiling approach to map Dnmt2 target sequences. The combined results will provide insights into the relevance of epigenetic mechanisms during germ line development.

生殖细胞通过将遗传信息传递给下一代来维持生命。生殖细胞有可能发育成任何组织，因此保护它们免受不适当的分化是至关重要的。提供这种保护的机制尚不清楚，可能与理解体细胞如何维持多能性有关。dna甲基化和组蛋白修饰在基因表达的表观遗传调控中起主要作用。我们将分析这些修饰在生殖细胞谱系与体细胞分离过程中的功能，它们的转录静止和在黑腹果蝇胚胎发育过程中的身份维持。宿主实验室已经确定Dnmt2负责果蝇基因组的dna甲基化，并且在极细胞（原始生殖细胞）中存在高水平的Dnmt2介导的甲基化。现在，我们将在全球范围内分析野生型胚胎和胚胎突变体发育中的生殖谢弗细胞中dna甲基化和其他表观遗传标记（共价组蛋白修饰）的动态，以寻找与建立和维持极细胞身份相关的基因。这将辅以基因组分析方法来绘制Dnmt2靶序列。综合结果将提供见解的相关性表观遗传机制在种系发育。