A regulatory role for repeated decoy transcription factor binding sites in target gene expression
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44320_2012_Article_BFMSB20127.pdf
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3.09 MB
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Author(s)
Lee, Tek‐Hyung
Maheshri, Narendra
Date Issued
March 27, 2012
Journal
Molecular Systems Biology
Publisher
Nature Publishing Group UK
Citation
Moleculr Systems Biol 8:576
Abstract
Tandem repeats of DNA that contain transcription factor (TF) binding sites could serve as decoys, competitively binding to TFs and affecting target gene expression. Using a synthetic system in budding yeast, we demonstrate that repeated decoy sites inhibit gene expression by sequestering a transcriptional activator and converting the graded dose–response of target promoters to a sharper, sigmoidal‐like response. On the basis of both modeling and chromatin immunoprecipitation measurements, we attribute the altered response to TF binding decoy sites more tightly than promoter binding sites. Tight TF binding to arrays of contiguous repeated decoy sites only occurs when the arrays are mostly unoccupied. Finally, we show that the altered sigmoidal‐like response can convert the graded response of a transcriptional positive‐feedback loop to a bimodal response. Together, these results show how changing numbers of repeated TF binding sites lead to qualitative changes in behavior and raise new questions about the stability of TF/promoter binding.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1038/msb.2012.7
