RT Journal A1 Lubliner, Shai A1 Regev, Ifat A1 Lotan-Pompan, Maya A1 Edelheit, Sarit A1 Weinberger, Adina A1 Segal, Eran T1 Core promoter sequence in yeast is a major determinant of expression level JF Genome Research JO Genome Research YR 2015 FD July 01 VO 25 IS 7 SP 1008 OP 1017 DO 10.1101/gr.188193.114 UL http://genome.cshlp.org/content/25/7/1008.abstract AB 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.