A regulatory role for repeated decoy transcription factor binding sites in target gene expression.
A regulatory role for repeated decoy transcription factor binding sites in target gene expression.
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DOI：
10.1038/msb.2012.7
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发表时间：
2012-03-27
影响因子：
9.9
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含有转录因子（TF）结合位点的DNA串联重复序列可以作为诱饵，竞争性地与TF结合并影响靶基因的表达。通过在出芽酵母中使用一个合成系统，我们证明了重复的诱饵位点通过隔离转录激活子和将目标启动子的梯度剂量反应转化为更尖锐的s型反应来抑制基因表达。在建模和染色质免疫沉淀测量的基础上，我们将改变的反应归因于TF结合诱饵位点，而不是启动子结合位点。紧密的TF结合到连续重复的诱饵位点阵列，只有当阵列大部分未被占用时才会发生。最后，我们证明了改变的s型响应可以将转录正反馈回路的分级响应转换为双峰响应。总之，这些结果显示了重复TF结合位点数量的变化如何导致行为的质变，并对TF/启动子结合的稳定性提出了新的问题。
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.