Understanding how precise control of gene expression is specified within regulatory DNA sequences is a key challenge with far-reaching implications. Many studies have focused on the regulatory role of transcription factor–binding sites. Here, we explore the transcriptional effects of different elements, nucleosome-disfavoring sequences and, specifically, poly(dA:dT) tracts that are highly prevalent in eukaryotic promoters. By measuring promoter activity for a large-scale promoter library, designed with systematic manipulations to the properties and spatial arrangement of poly(dA:dT) tracts, we show that these tracts significantly and causally affect transcription. We show that manipulating these elements offers a general genetic mechanism, applicable to promoters regulated by different transcription factors, for tuning expression in a predictable manner, with resolution that can be even finer than that attained by altering transcription factor sites. Overall, our results advance the understanding of the regulatory code and suggest a potential mechanism by which promoters yielding prespecified expression patterns can be designed.
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We wish to dedicate this paper to Jon Widom who inspired and assisted us greatly throughout this project. This work was supported by grants from the European Research Council (ERC) and the US National Institutes of Health (NIH) to E. Segal. E. Segal is the incumbent of the Soretta and Henry Shapiro career development chair. T.R.-S. and M.L. thank the Azrieli Foundation for the award of an Azrieli Fellowship. We thank G. Hornung for his help with the analysis of flow cytometry measurements and E. Mochly for his help with the preparation of Supplementary Figure 9.
The authors declare no competing financial interests.
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Raveh-Sadka, T., Levo, M., Shabi, U. et al. Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast. Nat Genet 44, 743–750 (2012) doi:10.1038/ng.2305
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