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播到下一代来维持生命。生殖细胞有可能发育成任何组织，因此至关重要的是保护它们免受不适当的分化。提供此保护的机制尚不清楚，并且可能与了解体细胞如何保持多能性有关。 DNA-甲基化和组蛋白修饰在基因表达的表观遗传调节中起主要作用。我们将分析这些修饰的功能，在生殖细胞谱系隔离时，它们的转录静止以及在果蝇果蝇胚胎发育期间的身份的维持。宿主实验室已经确定，DNMT2负责苍蝇基因组的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DNA-甲基化和其他表观遗传标记（共价组蛋白修饰）的动力学，以开发野生型胚胎和胚胎突变体的生殖细胞，以建立和维持极点细胞身份。这将通过绘制DNMT2目标序列的基因组分析方法来补充。结合结果将提供有关生殖线发育过程中表观遗传机制相关性的见解。