Analysis of the dynamics of epigenetic modifications during Drosophila 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。生殖细胞具有发育成任何组织的潜力，因此保护它们免于不适当的分化至关重要。提供这种保护的机制是未知的，可能与理解体干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控中起主要作用。我们将分析这些修改的功能，在分离的生殖细胞谱系从体细胞，转录静止和维护其身份在胚胎发育的果蝇。宿主实验室已经确定Dnmt 2负责果蝇基因组的DNA甲基化，并且高水平的Dnmt 2介导的甲基化存在于极细胞（原始生殖细胞）中。我们现在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）在野生型胚胎和胚胎突变体的生殖谢弗细胞中的动态，以确定和维持极细胞身份的基因。这将通过基因组分析方法来补充，以绘制Dnmt2靶序列。综合结果将提供深入了解生殖系发育过程中表观遗传机制的相关性。

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.