Genetic Silencing in Germline Maintenance and Function

描述（由申请人提供）：体内控制基因表达 涉及调节蛋白质复合物的多个层次， 与DNA的联系基因表达的顺序控制 胚胎发生已经进化到产生许多类似主题的变体， 每个物种的具体细节。在大多数后生动物中， 生殖细胞在整个发育过程和连续的世代中， 更新整个有机体的能力。因此，生殖细胞保持全能性。 全能性的保持似乎在许多动物中完成， 至少在一定程度上，是通过原始生殖细胞的精心安排， 再加上对大多数发育线索的固有反应迟钝。使用 线虫秀丽隐杆线虫作为模式系统，遗传和 分子方法将用于研究赋予和 保持生殖细胞的全能性。一个候选过程是基因沉默， 染色质这种表观遗传过程具有生殖细胞特异性的成分; 这些成分可能参与生殖细胞特性的维持。 C. elegans将被用来创建和分离 导致生殖细胞沉默缺陷的突变。突变将是 鉴定缺陷基因。这些的作用 将使用各种探针研究染色质组织中的基因 评估突变体对核小体组蛋白修饰的影响， 减数分裂期间染色体的相互作用。不同组件如何相互作用 也将决定如何安排沉默过程。人们希望 了解这些过程中的生殖谱系将提供一个 理解所有后代共有的潜在机制 这一创始血统。

DESCRIPTION (provided by applicant): Controlling gene expression in vivo involves regulating multiple hierarchies of protein complexes and their association with DNA. The sequential control of gene expression during embryogenesis has evolved to yield many variations of similar themes, with details that are specific to each species. In most metazoan animals, only the germ cells retain, throughout both development and successive generations, the ability to renew an entire organism. Germ cells therefore retain totipotency. The retention of totipotency appears to be accomplished in many animals, at least in part, by an orchestrated sequestration of the primordial germ cells, coupled with an inherent unresponsiveness to most developmental cues. Using the nematode Caenorhabditis elegans as a model system, a combination of genetic and molecular approaches will be used to investigate the processes that confer and maintain germ cell totipotency. One candidate process is genetic silencing of chromatin. This epigenetic process has components that are germ cell specific; these components likely participate in the maintenance of germ cell identity. The genetics available in C. elegans will be used to create and isolate mutations that cause defects in germ line silencing. The mutations will be characterized and the defective genes will be identified. The role of these genes in chromatin organization will be investigated using a variety of probes to assess the mutants' effects on nucleosomal histone modifications and chromosomal interactions during meiosis. How the different components interact to orchestrate the silencing process will also be determined. It is hoped that an understanding of these processes in the germ lineage will provide an understanding of the underlying mechanisms that are common to all descendents of this founding lineage.