Molecular and Genetic Analysis of Chromatin Structure

描述（由申请人提供）：真核生物染色体被细分为功能和结构自治域。这是在半个多世纪前对两栖动物卵母细胞的灯刷染色体和昆虫的多线染色体的细胞学研究中首次认识到的。最近，真核生物染色体结构域组织的令人信服的证据来自遗传、分子和生化实验的结合。这些研究表明，这种组织原理不仅对染色体在细胞核内的包装至关重要，而且对基因活性的适当调节也至关重要。真核生物染色体的细分需要一种分离结构域的机制。称为边界或绝缘体的特殊元件被认为是为了达到这个目的。作为染色质结构域边界的功能元素最初是在果蝇中发现的，现在在酵母、海胆、爪蟾、鸡、老鼠和人类等多种生物中都发现了这些元素。这些元件定义了染色体结构域的界限，并起着建立独立的基因活性单元的作用，将一个结构域内的基因或调控元件与相邻结构域外的调控元件的作用隔离开来。本提案的目的是表征几种果蝇边界和阐明其作用机制。

DESCRIPTION (provided by applicant): Eukaryotes chromosomes are subdivided into functionally and structurally autonomous domains. This was first recognized more than a half century ago in cytological studies on the lampbrush chromosomes of amphibian oocytes and the polytene chromosomes of insects. More recently, convincing evidence for the domain organization of eukaryotic chromosomes has come from a combination of genetic, molecular and biochemical experiments. These studies demonstrate that this organizing principle is of critical importance not only for the packaging of chromosomes inside the nucleus, but also for the proper regulation of gene activity. The subdivision of eukaryotic chromosome into domains requires a mechanism to separate one domain from another. Special elements called boundaries or insulators are thought to serve this purpose. Elements that function, as boundaries of chromatin domains were first identified in Drosophila, and they have now been found in a diverse array of organisms including yeast, sea urchins, Xenopus, chickens, mouse and humans. These elements define the limits of chromosomal domains and function to establish independent units of gene activity, insulating genes or regulatory elements within a domain from the action of regulatory elements located outside in adjacent domains. The aim of this proposal is to characterize several Drosophila boundaries and elucidate their mechanism of action.