The transcription factor titration effect dictates level of gene expression.

The transcription factor titration effect dictates level of gene expression.
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DOI:
10.1016/j.cell.2014.02.022
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发表时间:
2014-03-13
期刊:
影响因子:
64.5
通讯作者:
Phillips R
Phillips R
中科院分区:
生物学1区
文献类型:
--
作者:
Brewster RC;Weinert FM;Garcia HG;Song D;Rydenfelt M;Phillips R

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转录模型通常是围绕RNA聚合酶和转录因子(TF)作用于单个启动子拷贝的图像构建的。然而,大多数TF在具有不同结合亲和力的多个基因之间共享。除此之外,基因通常以高拷贝数存在;在染色体或质粒或病毒载体上以多个相同的拷贝存在,拷贝数为数百个。使用热力学模型,我们表征TF拷贝数和对TF的需求之间的相互作用。我们证明了该模型的无参数预测能力作为TF拷贝数和可用特异性结合位点的数量和亲和力的函数;这种预测控制对于理解转录和定量设计遗传电路输出的愿望是重要的。最后,我们利用这些实验来动态测量质粒在细胞周期中的拷贝数。
Models of transcription are often built around a picture of RNA polymerase and transcription factors (TFs) acting on a single copy of a promoter. However, most TFs are shared between multiple genes with varying binding affinities. Beyond that, genes often exist at high copy number; in multiple, identical copies on the chromosome or on plasmids or viral vectors with copy numbers in the hundreds. Using a thermodynamic model, we characterize the interplay between TF copy number and the demand for that TF. We demonstrate the parameter-free predictive power of this model as a function of the copy number of the TF and the number and affinities of the available specific binding sites; such predictive control is important for the understanding of transcription and the desire to quantitatively design the output of genetic circuits. Finally we use these experiments to dynamically measure plasmid copy number through the cell cycle.
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