Upstream stimulatory factor 2 stimulates transcription through an initiator element in the mouse cytochrome c oxidase...

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.