Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast.
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.
Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
Tali
T
Raveh-Sadka
Michal
M
Levo
Uri
U
Shabi
Boaz
B
Shany
Leeat
L
Keren
Maya
M
Lotan-Pompan
Danny
D
Zeevi
Eilon
E
Sharon
Adina
A
Weinberger
Eran
E
Segal
D001483:Base Sequence; D001665:Binding Sites; D004271:DNA, Fungal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics*
D004271:DNA, Fungal; D009707:Nucleosomes; D014157:Transcription Factors