Broad compatibility between yeast UAS elements and core promoters and identification of promoter elements that determine cofactor specificity

Three classes of yeast protein-coding genes are distinguished by their dependence on the transcription cofactors TFIID, SAGA, and Mediator (MED) Tail, but whether this dependence is determined by the core promoter, upstream activating sequences (UASs), or other gene features is unclear. Also unclear is whether UASs can broadly activate transcription from the different promoter classes. Here, we measure transcription and cofactor specificity for thousands of UAS-core promoter combinations and find that most UASs broadly activate promoters regardless of regulatory class, while few display strong promoter specificity. However, matching UASs and promoters from the same gene class is generally important for optimal expression. We find that sensitivity to rapid depletion of MED Tail or SAGA is dependent on the identity of both UAS and core promoter, while dependence on TFIID localizes to only the promoter. Finally, our results suggest the role of TATA and TATA-like promoter sequences in MED Tail function. [Display omitted] •Most yeast UASs can activate core promoters from differing regulatory classes•Transcription levels depend partly on matching UASs and promoters by regulatory class•Mediator Tail and SAGA specificity are dependent on both UAS and promoter identity•TFIID specificity is dependent primarily on core promoter identity Schofield and Hahn present a large-scale reporter assay measuring transcription of many combinations of yeast upstream activating sequences (UASs) and gene promoters. Their results suggest that UASs display both intrinsic activating potential and varying degrees of promoter specificity and that UASs and promoters both contribute to gene-specific regulation by transcriptional cofactors.