Analysis of combinatorial cis-regulation in synthetic and genomic promoters.
Analysis of combinatorial cis-regulation in synthetic and genomic promoters.
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DOI：
10.1038/nature07521
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发表时间：
2009-01-08
期刊：
影响因子：
64.8
通讯作者：
Cohen, Barak A.
中科院分区：
文献类型：
--
作者：
Gertz, Jason;Siggia, Eric D.;Cohen, Barak A.
转录因子结合位点（TFBS）正在迅速被发现。我们现在必须开始将注意力转向理解这些位点如何结合起来影响基因表达。从启动子序列准确预测基因表达的定量模型将是解决这一问题的关键部分。在这里，我们提出了这样一个模型的基础上分析合成启动子库在酵母中。热力学模型仅基于转录因子与DNA以及转录因子之间的平衡结合，捕获了每个文库中表达变化的很大一部分。这些库的热力学分析揭示了我们的系统中的几个现象，包括协同性和弱结合位点的影响。当应用于基因组，由Mig 1，这是训练合成启动子的抑制模型，预测了一些Mig 1调节的基因，缺乏显着的Mig 1结合位点在其启动子。热力学方法的成功表明，编码的顺式调控位点的组合的信息主要是通过简单的蛋白质-DNA和蛋白质-蛋白质相互作用与复杂的生化反应，如核小体修饰，下游事件的解释。定量分析的合成启动子库将是一个重要的工具，在解开规则的组合顺式调控。
Transcription factor binding sites (TFBS) are being discovered at a rapid pace. We must now begin to turn our attention towards understanding how these sites work in combination to influence gene expression. Quantitative models that accurately predict gene expression from promoter sequence will be a crucial part of solving this problem. Here we present such a model based on the analysis of synthetic promoter libraries in yeast. Thermodynamic models based only on the equilibrium binding of transcription factors to DNA and to each other captured a large fraction of the variation in expression in every library. Thermodynamic analysis of these libraries uncovered several phenomena in our system, including cooperativity and the effects of weak binding sites. When applied to the genome, a model of repression by Mig1, which was trained on synthetic promoters, predicts a number of Mig1 regulated genes that lack significant Mig1 binding sites in their promoters. The success of the thermodynamic approach suggests that the information encoded by combinations of cis-regulatory sites is interpreted primarily through simple protein-DNA and protein-protein interactions with complicated biochemical reactions, such as nucleosome modifications, being down stream events. Quantitative analyses of synthetic promoter libraries will be an important tool in unraveling the rules underlying combinatorial cis-regulation.
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影响因子：
9.9
作者：
Cox, Robert Sidney 3rd;Surette, Michael G;Elowitz, Michael B
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0407365101
发表时间：
2004-11-16
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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