TRANSCRIPTION FACTOR INTERACTIONS WITH NUCLEOSOMES

描述（改编自申请人摘要）：染色质的调节 结构在转录调控中起重要作用。这在很大程度 修饰发生在核小体的水平上，其结构抑制 许多核蛋白的结合和功能。核小体是由 由147个碱基对DNA包围的组蛋白核心。核小体 结构可以通过复合物如乙酰转移酶共价修饰 或去乙酰化酶，或通过与染色质修饰的 配合物这些复合物可以改变染色质，以创建结构， 允许因子结合和功能（“活化的”）或 不允许因子结合和功能（“抑制的”）。这些复合物 也在发育过程中维持基因表达模式中发挥作用， 有人建议他们通过建立激活或 在细胞分裂过程中被抑制的染色质状态。的 本申请的目的是详细研究 ATP依赖性染色质重塑复合物。这个庞大而多样化的群体， 复合物利用ATP水解的能量来修饰染色质结构 通过改变组蛋白-DNA接触、组蛋白-组蛋白 联系人或两者。研究者主要使用人类SWI/SNF 重塑复合体家族提出的实验将：1） 研究SWI/SNF功能的能量学，目标是开发和 如何使用ATP水解的能量来重塑 核小体结构; 2）使用诱变和交联来表征 核小体在重塑时发生的结构变化， 表征这些所需的组蛋白的部分， 结构变化; 3）比较和对比不同的功能 SWI/SNF复合物家族的成员之间以及与ISWI之间的相互作用 ATP依赖性重塑复合物家族。

DESCRIPTION (Adapted from the applicant's abstract): Modulation of chromatin structure plays an important role in transcriptional regulation. Much of this modification occurs at the level of the nucleosome, whose structure inhibits binding and function of numerous nuclear proteins. Nucleosomes are composed of a histone protein core surrounded by 147 base pairs of DNA. Nucleosome structure can be modified covalently, by complexes such as acetyltransferases or de-acetylases, or non-covalently via interactions with chromatin modifying complexes. These complexes can alter chromatin to create structures that are either permissive for factor binding and function ("activated") or non-permissive for factor binding and function ("repressed"). These complexes also play a role in maintaining gene expression patterns during development, and it has been proposed that they do this by establishing activated or repressed chromatin states that are maintained across cell division. The purpose of this application is to study in detail the mechanism of action of ATP-dependent chromatin remodeling complexes. This large and diverse group of complexes uses the energy of ATP hydrolysis to modify chromatin structure non-covalently by altering either histone-DNA contacts, histone-histone contacts, or both. The investigator works primarily with the human SWI/SNF family of remodeling complexes. Experiments are proposed that will: 1) investigate the energetics of SWI/SNF function, with the goal o developing an explicit model for how the energy of ATP hydrolysis is used to remodel nucleosome structure; 2) use mutagenesis and crosslinking to characterize the structural changes that occur to the nucleosome upon remodeling, and to characterize the portions of the histones that are required for these structural changes; and 3) compare and contrast the function of different members of the SWI/SNF family of complexes with each other and with the ISWI family of ATP-dependent remodeling complexes.