真核生物前起始复合物的全基因组结构受非共有蛋白-DNA结合的影响
Genome-wide organization of eukaryotic pre-initiation complex is influenced by nonconsensus protein-DNA binding
摘要：
真核前起始复合物（PIC）的关键组分的全基因组结合偏好最近已经由Rhee和Pugh在酿酒酵母中以高分辨率测量（Nature（2012）483：295-301）。然而，决定PIC结合特异性的规则仍然知之甚少。在这项研究中，我们表明，非共识蛋白质-DNA结合显着影响PIC结合偏好。我们估计，这种非共有结合在统计上至少贡献2-3千卡/摩尔（平均）的额外的吸引力的自由能每个蛋白质，每个核心启动子区域。预测的吸引力的影响是特别强的重复聚（dA：dT）和聚（dC：dG）tracts。总的来说，计算的非共有蛋白质-DNA结合的自由能景观显示出与测量的全基因组PIC占有率的强相关性。值得注意的是，TFIID主导和SAGA主导基因的统计PIC结合偏好与非共有自由能景观相关，但这两组基因是基于平均自由能谱可区分的。我们认为，预测的非共识的结合机制提供了一个全基因组的背景下，特定的启动子元件，如转录因子结合位点，TATA样元素，和特异性结合的PIC组件的核小体。我们还表明，非共识结合影响转录频率全基因组。
英文摘要：
Genome-wide binding preferences of the key components of eukaryotic pre-initiation complex (PIC) have been recently measured with high resolution in Saccharomyces cerevisiae by Rhee and Pugh (Nature (2012) 483:295-301). Yet the rules determining the PIC binding specificity remain poorly understood. In this study we show that nonconsensus protein-DNA binding significantly influences PIC binding preferences. We estimate that such nonconsensus binding contribute statistically at least 2-3 kcal/mol (on average) of additional attractive free energy per protein, per core promoter region. The predicted attractive effect is particularly strong at repeated poly(dA:dT) and poly(dC:dG) tracts. Overall, the computed free energy landscape of nonconsensus protein-DNA binding shows strong correlation with the measured genome-wide PIC occupancy. Remarkably, statistical PIC binding preferences to both TFIID-dominated and SAGA-dominated genes correlate with the nonconsensus free energy landscape, yet these two groups of genes are distinguishable based on the average free energy profiles. We suggest that the predicted nonconsensus binding mechanism provides a genome-wide background for specific promoter elements, such as transcription factor binding sites, TATA-like elements, and specific binding of the PIC components to nucleosomes. We also show that nonconsensus binding influences transcriptional frequency genome-wide.
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