Mizuno T, Harashima S
Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita-shi, Japan.
Mol Gen Genet. 2000 Feb;263(1):48-59. doi: 10.1007/pl00008675.
The Saccharomyces cerevisiae protein Sin4 has been suggested to affect the transcription of various genes by locally altering chromatin structure. Previous studies have defined two classes of promoters: those which are activated by loss of SIN4 function (termed sin4-responsive promoters) and those which are not activated by sin4 mutations (termed sin4 non-responsive promoters). We analyzed the mechanism of this differential response of the two classes of promoters to a sin4 mutation. The sin4 non-responsive promoters were activated when upstream elements in the promoter region were eliminated. The upstream elements of sin4 non-responsive promoters were, in turn, found to repress the activity of the sin4-responsive promoters in an orientation-independent manner. The sin4-mediated activation was repressed by the Rme1- but not by the Tup1-Ssn6-mediated repression system. Activation of sin4-responsive promoters by Pho4 and the sin4 mutation was additive, and enhancement of transcription driven by sin4-responsive promoters was found to be due to an increase in the basal rate of transcription. The upstream regions in the sin4 non-responsive promoters contained elements that were able to inhibit activation of basal transcription. Based on these observations, we suggest that activation of basal transcription by a mutation in a gene for a global repressor, SIN4, occurs through a mechanism that differs from that responsible for activator-mediated transcriptional enhancement, and we therefore propose that basal transcription and activator-mediated transcription are repressed by different mechanisms.
酿酒酵母蛋白Sin4被认为可通过局部改变染色质结构来影响各种基因的转录。先前的研究定义了两类启动子:一类是因SIN4功能缺失而被激活的启动子(称为sin4反应型启动子),另一类是不被sin4突变激活的启动子(称为sin4无反应型启动子)。我们分析了这两类启动子对sin4突变产生不同反应的机制。当启动子区域的上游元件被去除时,sin4无反应型启动子被激活。反过来,sin4无反应型启动子的上游元件被发现以不依赖方向的方式抑制sin4反应型启动子的活性。sin4介导的激活被Rme1抑制,但不被Tup1-Ssn6介导的抑制系统抑制。Pho4和sin4突变对sin4反应型启动子的激活具有累加效应,并且发现sin4反应型启动子驱动的转录增强是由于基础转录速率的增加。sin4无反应型启动子的上游区域含有能够抑制基础转录激活的元件。基于这些观察结果,我们认为全局阻遏物基因SIN4中的突变对基础转录的激活是通过一种不同于激活剂介导的转录增强机制发生的,因此我们提出基础转录和激活剂介导的转录是通过不同机制被抑制的。