Breen G A, Jordan E M
Department of Molecular and Cell Biology, The University of Texas at Dallas, P.O. Box 830688, Richardson, TX 75083-0688, USA.
Biochim Biophys Acta. 2000 Dec 15;1517(1):119-27. doi: 10.1016/s0167-4781(00)00269-4.
Upstream stimulatory factor (USF) is a basic helix-loop-helix-leucine zipper transcription factor that plays an important role in transcriptional activation and cell proliferation. In this article, we demonstrate that the mouse cytochrome c oxidase subunit Vb gene (Cox5b) can be transactivated by ectopic expression of USF2 through an initiator (Inr) element in the core promoter. Importantly, using a dominant-negative mutant of USF2, we demonstrate the role of endogenous USF2 proteins in the transcriptional activation of the Cox5b Inr. Domains of USF2 encoded by exon 4, exon 5 and the USF-specific region are important for maximum activation of the Cox5b Inr. Using the adenovirus E1A oncoprotein, we show that p300/CBP acts as a coactivator in the USF2-dependent activation of the Cox5b Inr. We also demonstrate that although expression of multifunctional regulatory factor, Yin Yang 1 (YY1), can stimulate transcription of the Cox5b Inr to a modest extent, expression of YY1 together with USF2 greatly reduces the level of activation of the Cox5b Inr. Furthermore, we show that the transcription factor, Sp1, represses both the YY1- and the USF2-dependent activation of the Cox5b Inr, indicating competition among Sp1, YY1, and USF2.
上游刺激因子（USF）是一种碱性螺旋-环-螺旋-亮氨酸拉链转录因子，在转录激活和细胞增殖中起重要作用。在本文中，我们证明小鼠细胞色素c氧化酶亚基Vb基因（Cox5b）可通过核心启动子中的起始子（Inr）元件被USF2的异位表达反式激活。重要的是，使用USF2的显性负性突变体，我们证明了内源性USF2蛋白在Cox5b Inr转录激活中的作用。由外显子4、外显子5和USF特异性区域编码的USF2结构域对于Cox5b Inr的最大激活很重要。使用腺病毒E1A癌蛋白，我们表明p300/CBP在USF2依赖的Cox5b Inr激活中作为共激活因子起作用。我们还证明，尽管多功能调节因子阴阳1（YY1）的表达可在一定程度上刺激Cox5b Inr的转录，但YY1与USF2一起表达会大大降低Cox5b Inr的激活水平。此外，我们表明转录因子Sp1抑制YY1和USF2依赖的Cox5b Inr激活，表明Sp1、YY1和USF2之间存在竞争。
