title: Core promoter sequence in yeast is a major determinant of expression level.
abstract: The core promoter is the regulatory sequence to which RNA polymerase is recruited and where it acts to initiate transcription. Here, we present the first comprehensive study of yeast core promoters, providing massively parallel measurements of core promoter activity and of TSS locations and relative usage for thousands of native and designed sequences. We found core promoter activity to be highly correlated to the activity of the entire promoter and that sequence variation in different core promoter regions substantially tunes its activity in a predictable way. We also show that location, orientation, and flanking bases critically affect TATA element function, that transcription initiation in highly active core promoters is focused within a narrow region, that poly(dA:dT) orientation has a functional consequence at the 3' end of promoters, and that orthologous core promoters across yeast species have conserved activities. Our results demonstrate the importance of core promoters in the quantitative study of gene regulation.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 7610001 Rehovot, Israel;
authors.forename: Shai
authors.initials: S
authors.lastname: Lubliner
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel;
authors.forename: Ifat
authors.initials: I
authors.lastname: Regev
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel;
authors.forename: Maya
authors.initials: M
authors.lastname: Lotan-Pompan
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Edelheit
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel;
authors.forename: Adina
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel;
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
mesh_terms: D015966:Gene Expression Regulation, Fungal; D023281:Genomics; D011401:Promoter Regions, Genetic; D016385:TATA Box; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D015003:Yeasts / Q000235:genetics*