Prochasson Philippe, Neely Kristen E, Hassan Ahmed H, Li Bing, Workman Jerry L
Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biology, 306 Althouse Laboratory, The Pennsylvania State University, University Park, PA 16802, USA.
Mol Cell. 2003 Oct;12(4):983-90. doi: 10.1016/s1097-2765(03)00366-6.
The SWI/SNF complex is required for the expression of many yeast genes. Previous studies have implicated DNA binding transcription activators in targeting SWI/SNF to UASs and promoters. To determine how activators interact with the complex and to examine the importance of these interactions, relative to other potential targeting mechanisms, for SWI/SNF function, we sought to identify and mutate the activator-interaction domains in the complex. Here we show that the N-terminal domain of Snf5 and the second quarter of Swi1 are sites of activation domain contact. Deletion of both of these domains left the SWI/SNF complex intact but impaired its ability to bind activation domains. Importantly, while deletion of either domain alone had minor phenotypic effect, deletion of both resulted in strong SWI/SNF related phenotypes. Thus, two distinct activator-interaction domains play overlapping roles in the targeting activity of SWI/SNF, which is essential for its function in vivo.
许多酵母基因的表达需要SWI/SNF复合物。先前的研究表明,DNA结合转录激活因子将SWI/SNF靶向到上游激活序列(UASs)和启动子。为了确定激活因子如何与该复合物相互作用,并检验相对于其他潜在靶向机制而言,这些相互作用对SWI/SNF功能的重要性,我们试图鉴定并突变该复合物中与激活因子相互作用的结构域。在此我们表明,Snf5的N端结构域和Swi1的第二个四分之一区域是与激活结构域接触的位点。删除这两个结构域后,SWI/SNF复合物仍保持完整,但削弱了其结合激活结构域的能力。重要的是,虽然单独删除任何一个结构域都只有轻微的表型效应,但同时删除两者则导致强烈的SWI/SNF相关表型。因此,两个不同的与激活因子相互作用的结构域在SWI/SNF的靶向活性中发挥重叠作用,这对其在体内的功能至关重要。