A systems approach to measuring the binding energy landscapes of transcription factors
A systems approach to measuring the binding energy landscapes of transcription factors
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DOI：
10.1126/science.1131007
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发表时间：
2007-01-12
期刊：
影响因子：
56.9
通讯作者：
Quake, Stephen R.
中科院分区：
文献类型：
--
作者：
Maerkl, Sebastian J.;Quake, Stephen R.
系统生物学的主要目标是预测生物网络的功能。尽管在许多情况下已经成功确定了网络拓扑，但管理这些网络的定量参数通常没有。测量以高通量格式的分子相互作用的亲和力仍然有问题，尤其是对于短暂和低亲和力相互作用。我们描述了一个高通量微流体平台，该平台根据分子相互作用的机械捕获来测量此类性能。在这个平台的情况下，我们表征了四个真核转录因子的DNA结合能景观。这些景观用于测试有关转录因子结合的基本假设，并预测其体内功能。
A major goal of systems biology is to predict the function of biological networks. Although network topologies have been successfully determined in many cases, the quantitative parameters governing these networks generally have not. Measuring affinities of molecular interactions in high-throughput format remains problematic, especially for transient and low-affinity interactions. We describe a high-throughput microfluidic platform that measures such properties on the basis of mechanical trapping of molecular interactions. With this platform we characterized DNA binding energy landscapes for four eukaryotic transcription factors; these landscapes were used to test basic assumptions about transcription factor binding and to predict their in vivo function.