Genetic Silencing in Germline Maintenance and Function

种系维持和功能中的基因沉默

• 批准号: 6698565
• 负责人: William G. KELLY
• 金额: $ 25.84万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6698565
• 关键词: Caenorhabditis elegans; chromatin; cytogenetics; eukaryote; gene expression; gene induction /repression; gene mutation; genetic transcription; germ cells; histones; meiosis; microarray technology; molecular biology; molecular cloning; sex chromosomes

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.

描述(申请人提供)：体内基因表达调控 涉及调节蛋白质复合体的多个层次及其 与DNA的联系。基因表达的顺序调控 胚胎发生已经进化出许多相似主题的变体， 特定于每个物种的详细信息。在大多数后生动物中，只有 生殖细胞在整个发育和接续的世代中都保持着 更新整个生物体的能力。因此，生殖细胞保持全能性。 在许多动物中，全能性的保持似乎是在 至少部分是通过对原始生殖细胞的精心安排的隔离， 再加上对大多数发育线索的天生反应迟钝。使用 线虫秀丽线虫作为模式系统，结合了遗传和 分子方法将被用来研究赋予和 保持生殖细胞的全能性。一个候选过程是基因沉默 染色质。这一表观遗传过程含有生殖细胞特有的成分； 这些成分可能参与维持生殖细胞的特性。 线虫可利用的遗传学将被用于创造和分离 导致生殖系沉默缺陷的突变。突变将会是 特征和缺陷基因将被识别。这些因素的作用 染色质组织中的基因将使用各种探针进行研究 为了评估突变体对核小体组蛋白修饰的影响， 减数分裂过程中的染色体相互作用。不同组件如何交互 协调沉默的过程也将被确定。人们希望， 对生殖细胞谱系中这些过程的理解将提供一个 对所有后代共有的潜在机制的理解 这一创始血统的。