Abstract:
:Transcription factors (TFs) are key mediators that propagate extracellular and intracellular signals through to changes in gene expression profiles. However, the rules by which promoters decode the amount of active TF into target gene expression are not well understood. To determine the mapping between promoter DNA sequence, TF concentration, and gene expression output, we have conducted in budding yeast a large-scale measurement of the activity of thousands of designed promoters at six different levels of TF. We observe that maximum promoter activity is determined by TF concentration and not by the number of binding sites. Surprisingly, the addition of an activator site often reduces expression. A thermodynamic model that incorporates competition between neighboring binding sites for a local pool of TF molecules explains this behavior and accurately predicts both absolute expression and the amount by which addition of a site increases or reduces expression. Taken together, our findings support a model in which neighboring binding sites interact competitively when TF is limiting but otherwise act additively.
journal_name
Genome Resjournal_title
Genome researchauthors
van Dijk D,Sharon E,Lotan-Pompan M,Weinberger A,Segal E,Carey LBdoi
10.1101/gr.212316.116subject
Has Abstractpub_date
2017-01-01 00:00:00pages
87-94issue
1eissn
1088-9051issn
1549-5469pii
gr.212316.116journal_volume
27pub_type
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