RT Journal Article SR Electronic T1 Broad compatibility between yeast UAS elements and core promoters and identification of promoter elements that determine cofactor specificity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.03.515066 DO 10.1101/2022.11.03.515066 A1 Jeremy A. Schofield A1 Steven Hahn YR 2022 UL http://biorxiv.org/content/early/2022/11/04/2022.11.03.515066.abstract AB Three general classes of yeast protein-coding genes are distinguished by their dependence on the transcription cofactors TFIID, SAGA and Mediator (MED) Tail, but little is known about whether this dependence is determined by the core promoter, Upstream activation sites (UASs), or other gene features. It is also unclear whether UASs can broadly activate transcription from the different promoter classes or whether efficient transcription requires matching UASs and promoters of similar gene class. Here we measure transcription and cofactor specificity for tens of thousands of UAS-core promoter combinations. We find that <5% of UASs display strong core promoter specificity while most UASs can broadly activate promoters regardless of regulatory class. However, we find that matching UASs and promoters from the same gene class is generally important for optimal expression. From examining the cofactor dependence of this large UAS-promoter set, we find that sensitivity to rapid depletion of MED Tail or SAGA is dependent on the identity of both UAS and promoter while dependence on TFIID localizes to only the core promoter. Our results explain why transcription factor-mediated MED recruitment to the UAS does not always result in Tail-dependent transcription and highlight the role of TATA and TATA-like promoter sequences in MED Tail function.Competing Interest StatementThe authors have declared no competing interest.