DNA determinants for chromatin modifiers in yeast

描述（由申请人提供） 一个需要理解的重要生物学问题是， ATP依赖性染色质重塑复合物靶向于特定的 发起人。因此，本研究提案的一个具体目的是阐明 复杂募集的分子机制。它正在迅速成为 了解这种瞄准过程至关重要，因为 大量科学发现将改变的染色质重塑联系起来 功能与癌症。为便于理解复杂的征聘工作， 芽殖酵母，酿酒酵母，将被用作模式生物。 鉴于其遗传上的易处理性，酵母是一种有吸引力的有机体， 研究染色质结构修饰剂的潜在分子机制。 此外，还对S.酿酒酵母已经被测序， 允许使用全基因组DNA微阵列技术的能力。的 通过这项技术获得的初步数据将允许全球 鉴定与特异性染色质修饰剂相关的启动子， 将导致以下问题：需要什么启动子序列 招聘一个特定的修改活动？这个基本但关键的 机制问题可以通过启动子缺失分析来回答， 构建异源启动子，并详细分析启动子 染色质结构一旦这些复合物的分子靶向被牢固地 理解，未来的实验可以提出，以确定参与 ATP依赖性染色质重塑与癌症的复合物。

DESCRIPTION (provided by applicant) A significant biological question that needs to be understood is how ATP-dependent chromatin remodeling complexes are targeted to specific promoters. Therefore, a specific aim of this research proposal is to elucidate the molecular mechanism(s) of complex recruitment. It is rapidly becoming paramount to understand this targeting process since there has been an explosion of scientific discoveries linking altered chromatin-remodeling function with cancer. To facilitate the understanding of complex recruitment, the budding yeast, Saccharomyces cerevisiae, will be used as a model organism. Given its genetic tractability, yeast is an appealing organism with which to study the underlying molecular mechanisms of modifiers of chromatin structure. Moreover, the complete genome of S. cerevisiae has been sequenced and this allows for the ability to employ genome-wide DNA microarray technology. The preliminary data obtained by this technique will allow for the global identification of promoters associated with specific chromatin modifiers which will lead to the following question: what promoter sequences are required for recruitment of a given modifying activity? This fundamental but critical mechanistic question can be answered by promoter deletion analysis, construction of heterologous promoters, and detailed analysis of promoter chromatin structure. Once the molecular targeting of these complexes is firmly understood, future experiments can be proposed to determine the involvement of ATP-dependent chromatin remodeling complexes with cancer.