Upstream Stimulatory Factor 2 Activates the Mammalian F1F0 ATP Synthase α-Subunit Gene Through an Initiator Element

• Published in: Gene expression 1998-01, Vol.7 (3), p.163-170
• Main Authors: BREEN, GAIL A. M., JORDAN, ELZORA M.
• Format: Article
• Language: English
• Subjects: Animals; Atp Synthase; Atpa Gene; Base Sequence; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Erythroid-Specific DNA-Binding Factors; Genes, Dominant; Humans; Initiator Element; Mammals; Molecular Sequence Data; Mutation; Promoter Regions, Genetic; Proton-Translocating ATPases - genetics; Proton-Translocating ATPases - metabolism; Regulatory Sequences, Nucleic Acid; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Upstream Stimulatory Factor 2; Upstream Stimulatory Factors; YY1 Transcription Factor
• ISSN: 1052-2166; 1555-3884

The F1F0 ATP synthase is the central enzyme complex of the mitochondrial oxidative phosphorylation system synthesizing ATP from ADP and Pi. Our laboratory has been studying the transcriptional regulation of the nuclear gene that encodes the α-subunit of the mammalian mitochondrial ATP synthase complex (ATPA). We have previously identified an initiator element in the core promoter that plays an important role in expression of this gene. In this article, we demonstrate that ectopic expression of the transcription factor, upstream stimulatory factor 2 (USF2), transactivates the ATPA gene through this initiator element. Importantly, cotransfection of a dominant-negative USF2 mutant significantly reduces both the basal activity and the level of activation of the ATPA initiator by coexpressed USF2 demonstrating the role of endogenous USF2 proteins in this activation. We also identify several nucleotides in the ATPA initiator element that are important for both basal activity and USF2-dependent transactivation. We have also previously determined that the binding of the multifunctional regulatory protein, YY1, to this initiator element can positively regulate the ATPA gene. Here, we show that expression of YY1 together with USF2 results in a decreased level of activation of the ATPA initiator relative to expression of USF2 alone, suggesting competition between these two regulatory proteins.