Transcriptional activation of the F(1)F(0) ATP synthase alpha-subunit initiator element by USF2 is mediated by p300

We have been studying the transcriptional regulation of the mammalian F(1)F(0) ATP synthase alpha-subunit gene (ATPA), a TATA-less initiator-containing gene. We have previously determined that the transcription factor, upstream stimulatory factor 2 (USF2), can activate the ATPA gene through an initiator element in the core promoter. Here, we demonstrate that the coactivator p300 interacts functionally with USF2 proteins to potentiate the activation of the ATPA initiator element by USF2. The physiological relevance of this interaction was shown in vivo by expression of the adenovirus E1A oncoprotein. Wild-type E1A, but not E1A mutants that lacked p300-binding sites, inhibited the USF2-dependent transactivation of the ATPA initiator element. Furthermore, overexpression of p300 could reverse the inhibitory effect of E1A. Collectively, our results indicate that the USF2-dependent transcriptional activation of the ATPA initiator element is mediated by p300.