Studies of transvection and chromatin in Drosophila melanogaster

9511808 Wu在果蝇中已经鉴定了一个假定的染色质复合体的几个候选成员。 这些包括zeste的产物、后性梳、zeste的抑制子2、Polycomb、Polycomb-like和polyhomeotic）。 遗传学、生物化学和细胞学的数据证明了其他成员和其他类型的复合体的存在。 其他成员是谁？ 还有哪些复合体，其他复合体的成员是谁？ 这些都是重要的问题，因为一个复合体的影响是其所有成员活动的总和，在了解其所有组成部分之前，不可能了解一个复合体。 本建议涉及这些问题。 寻找染色质相关基因的基因筛选几乎完全依赖于四种现象：PFV，zeste 1眼睛颜色，同源异型和剂量补偿。 很明显，这些现象不能代表所有的发展计划。 因此，我们对染色质调节基因表达的蛋白质和机制的了解有限，几乎可以肯定的是，还有更多染色质相关的蛋白质和过程有待发现。例如，在被认为参与一种染色质复合物的12-17种蛋白质中，只有不到一半被鉴定出来。 因此，该提案的目标是确定迄今为止一直逃避研究人员的染色质相关基因和机制。 所提出的研究策略是通过实施三种新的筛选编码染色质相关功能的基因来实现遗传方法的多样化。 我们的筛选与大多数（如果不是全部的话）以前的筛选不同，以前的筛选通过改变特定表型（如眼睛颜色或片段身份）的突变来识别基因。 相反，我们的筛选将通过基因与染色质蛋白质的一些最佳候选者的相互作用或冗余来识别基因。 染色质结构是遗传和基因表达等基本现象的基础。 它参与转录、位置效应、重组和肿瘤发生，仅举几个例子。 这个提议探讨了果蝇染色质的结构。 ***

9511808 Wu Several candidate members of a putative chromatin complex have been identified in Drosophila. These include the products of zeste, Posterior sex combs, Suppressor 2 of zeste, Polycomb, Polycomb-like, and polyhomeotic). Genetic, biochemical, and cytological data argue for the existence of other members as well as for other types of complexes. Who are the other members? What other complexes are there and who are the members of the other complexes? These are important questions because the impact of a complex is the sum of the activities of all its members and it is not possible to fathom a complex until all its components are understood. This proposal address these questions. Genetic screens to find chromatin-related genes have relied almost exclusively on four phenomena: PFV, zeste1 eye color, homeosis, and dosage compensation. Clearly, these phenomena fall short of representing the full range of developmental programs. As a consequence, our understanding of the proteins and mechanisms by which chromatin regulates gene expression is limited and it is almost certain that more chromatin-related proteins and processes remain to be discovered. For example, of the 12-17 proteins thought to participate in one species of chromatin complex, less than half have been identified. The goal of the proposal is, therefore, to identify the chromatin-related genes and mechanisms that have managed thus far to elude researchers. The strategy of the proposed research is to diversify the genetic approach by implementing three new kinds of screens for genes encoding chromatin-related functions. Our screens are unlike most, if not all, previous screens which identified genes by mutations that modified specific phenotypes, such as eye color or segment identity. Instead, our screens will identify genes by virtue of their interaction or redundancy with some of our best candidates for chromatin proteins. %%% Chromatin structure underlies phenomena as fundamental as inheritance and gene expressio n. It is involved in transcription, position effects, recombination, and oncogenesis, to mention just a few examples. This proposal explores the structure of chromatin in Drosophila. ***