SNF/SWI COMPLEX AND TRANSCRIPTIONAL ACTIVATION

转录激活涉及基因和蛋白质之间复杂的相互作用。 特定的激活物、通用转录装置和染色质。 在酿酒酵母中，SNF/SWI复合体具有重要的 在这一过程中发挥作用，是转录激活所必需的 不同的基因。SNF/SWI复合体通过基因特异性激活 调节蛋白，并参与染色质的重塑 克服染色质介导的抑制。该建筑群由11个人组成 蛋白质(包括SWI1/ADR6、SNF2/SWI2、SWI3、SNF5、SNF6和SNF11)和 在真核生物中被广泛保守。同源蛋白质已经被 在果蝇和哺乳动物中发现了一个类似的复合体 从人类身上提纯的。在酵母系统中，遗传途径可以是 应用于提供对生理上重要的功能的洞察 SVF/SWI复合体。这项建议侧重于分析 在体内与其他蛋白质的复合体。其中三个项目涉及 先前双杂交中鉴定的蛋白质的功能特性 用于与SNF2交互的屏幕。第一种相互作用的蛋白质， MSN1，是基因特异性转录之间的接头候选 激活剂和特种部队/特种部队复合体。对MSN1的深入分析将是 对该模型进行了测试。第二，编码催化的基因 在双杂交中恢复了cAMP依赖的蛋白激酶亚基 筛选，以及该激酶活性与SNF/SWI复合体的关系 将会被评估。第三，七种尚未确定的相互作用蛋白 将以获得对SNF/SWI的新见解为目标 功能。最后，分析了互联网的功能和相互作用。 SNF6蛋白将被启动。遗传学证据表明SNF6具有 与其他SNF/SWI组件不同的角色，并可能相互作用 直接与基本转录因子结合。拟议的工作将进一步 我们对两者之间功能相互作用的理解 SNF/SWI复合体、转录因子和染色质成分 其天然染色体中启动子的转录激活 背景。

Transcriptional activation involves a complex interplay between gene- specific activators, the general transcription apparatus, and chromatin. In the yeast Saccharomyces cerevisiae, the SNF/SWI complex has an important role in this process and is required for transcriptional activation of diverse genes. The SNF/SWI complex facilitates activation by gene-specific regulatory proteins and has been implicated in remodeling chromatin to overcome chromatin-mediated repression. The complex comprises eleven proteins (including SWI1/ADR6, SNF2/SWI2, SWI3, SNF5, SNF6 and SNF11) and has been widely conserved in eukaryotes. Homologous proteins have been identified in Drosophila and mammals, and a similar complex has been purified from human. In the yeast system, genetic approaches can be applied to provide insight into physiologically important functions of the SVF/SWI complex. This proposal focuses on analysis of the interactions of the complex with other proteins in vivo. Three of the projects concern functional characterization of proteins identified in a previous two-hybrid screen for interaction with SNF2. First one of these interacting proteins, MSN1, is a candidate for an adaptor between gene specific transcriptional activators and the SNF/SWI complex. An intensive analysis of MSN1 will be carried out to test this model. Second, genes encoding the catalytic subunits of cAMP-dependent protein kinase were recovered in the two-hybrid screen, and the relationship of this kinase activity to the SNF/SWI complex will be assessed. Third, seven as yet unidentified interacting proteins will be characterized with the goal of obtaining new insights into SNF/SWI function. Finally, an analysis of the function and interactions of the SNF6 protein will be initiated. Genetics evidence suggests that SNF6 has a distinct role from other SNF/SWI components and perhaps interacts directly with basal transcription factors. The proposed work will further our understanding of the functional interactions that occur between the SNF/SWI complex, transcription factors, and chromatin components during transcriptional activation of promoters in their native chromosomal context.