Synergistic transcriptional-activation by the papillomavirus E2 protein occurs after DNA binding and correlates with...

The papillomavirus E2 protein only activates transcription strongly when two or more of its binding-sites, each of which bind an E2 dimer, are present upstream of a minimal promoter. Such synergy has been observed both in mammalian and yeast cells. In an attempt to understand the molecular basis of this synergy we carried out genomic footprinting to monitor the binding in vivo of native or mutant E2 proteins to different templates in yeast. We show that in vivo E2 binds to its site even under conditions where it does not activate a reporter gene. Binding occurs at each site independently of the number of sites and even in the absence of the activation domain. In contrast, analysis of the chromatin structure around the E2 binding-site(s) showed that a pronounced change in chromatin structure occurs under conditions in which E2 dimers activate transcription synergistically.