A regulatory role for repeated decoy transcription factor binding sites in target gene expression
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...
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| Format: | Article |
| Language: | English |
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Springer Nature
2012-03-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2012.7 |
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| _version_ | 1850179492103847936 |
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| author | Tek‐Hyung Lee Narendra Maheshri |
| author_facet | Tek‐Hyung Lee Narendra Maheshri |
| author_sort | Tek‐Hyung Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bb0f1b5bc7c64d0982a00a78c2fa64b9 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2012-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-bb0f1b5bc7c64d0982a00a78c2fa64b92025-08-20T02:18:28ZengSpringer NatureMolecular Systems Biology1744-42922012-03-018111110.1038/msb.2012.7A regulatory role for repeated decoy transcription factor binding sites in target gene expressionTek‐Hyung Lee0Narendra Maheshri1Department of Chemical Engineering, Massachusetts Institute of TechnologyDepartment of Chemical Engineering, Massachusetts Institute of TechnologyAbstract 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.https://doi.org/10.1038/msb.2012.7bimodalitytandem repeatstranscription factor decoystranscriptional regulation |
| spellingShingle | Tek‐Hyung Lee Narendra Maheshri A regulatory role for repeated decoy transcription factor binding sites in target gene expression Molecular Systems Biology bimodality tandem repeats transcription factor decoys transcriptional regulation |
| title | A regulatory role for repeated decoy transcription factor binding sites in target gene expression |
| title_full | A regulatory role for repeated decoy transcription factor binding sites in target gene expression |
| title_fullStr | A regulatory role for repeated decoy transcription factor binding sites in target gene expression |
| title_full_unstemmed | A regulatory role for repeated decoy transcription factor binding sites in target gene expression |
| title_short | A regulatory role for repeated decoy transcription factor binding sites in target gene expression |
| title_sort | regulatory role for repeated decoy transcription factor binding sites in target gene expression |
| topic | bimodality tandem repeats transcription factor decoys transcriptional regulation |
| url | https://doi.org/10.1038/msb.2012.7 |
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