The Schizosaccharomyces pombe inv1+ Regulatory Region Is Unusually Large and Contains Redundant cis-Acting Elements That Function in a SAGA- and Swi/Snf-Dependent Fashion

The Schizosaccharomyces pombe inv1+ gene encodes invertase, the enzyme required for hydrolysis of sucrose and raffinose. Transcription of inv1+ is regulated by glucose levels, with transcription tightly repressed in high glucose and strongly induced in low glucose. To understand this regulation, we have analyzed the inv1+ cis-regulatory region and the requirement for the trans-acting coactivators SAGA and Swi/Snf. Surprisingly, deletion of the entire 1-kilobase intergenic region between the inv1+ TATA element and the upstream open reading frame SPCC191.10 does not significantly alter regulation of inv1+ transcription. However, a longer deletion that extends through SPCC191.10 abolishes inv1+ induction in low glucose. Additional analysis demonstrates that there are multiple, redundant regulatory regions spread over 1.5 kb 5′ of inv1+, including within SPCC191.10, that can confer glucose-mediated transcriptional regulation to inv1+. Furthermore, SPCC191.10 can regulate inv1+ transcription in an orientation-independent fashion and from a distance as great as 3 kb. With respect to trans-acting factors, both SAGA and Swi/Snf are recruited to SPCC191.10 and to other locations in the large inv1+ regulatory region in a glucose-dependent fashion, and both are required for inv1+ derepression. Taken together, these results demonstrate that inv1+ regulation in S. pombe occurs via the use of multiple regulatory elements and that activation can occur over a great distance, even from elements within other open reading frames.