Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Biophys J. 2011 Nov 16;101(10):2465-75. doi: 10.1016/j.bpj.2011.10.012. Epub 2011 Nov 15.
Quantitative understanding of the principles regulating nucleosome occupancy on a genome-wide level is a central issue in eukaryotic genomics. Here, we address this question using budding yeast, Saccharomyces cerevisiae, as a model organism. We perform a genome-wide computational analysis of the nonspecific transcription factor (TF)-DNA binding free-energy landscape and compare this landscape with experimentally determined nucleosome-binding preferences. We show that DNA regions with enhanced nonspecific TF-DNA binding are statistically significantly depleted of nucleosomes. We suggest therefore that the competition between TFs with histones for nonspecific binding to genomic sequences might be an important mechanism influencing nucleosome-binding preferences in vivo. We also predict that poly(dA:dT) and poly(dC:dG) tracts represent genomic elements with the strongest propensity for nonspecific TF-DNA binding, thus allowing TFs to outcompete nucleosomes at these elements. Our results suggest that nonspecific TF-DNA binding might provide a barrier for statistical positioning of nucleosomes throughout the yeast genome. We predict that the strength of this barrier increases with the concentration of DNA binding proteins in a cell. We discuss the connection of the proposed mechanism with the recently discovered pathway of active nucleosome reconstitution.
在真核基因组学中，定量理解调控核小体占据基因组全谱的原理是一个核心问题。在这里，我们以酿酒酵母（Saccharomyces cerevisiae）作为模型生物来解决这个问题。我们对非特异性转录因子（TF）-DNA 结合自由能景观进行了全基因组的计算分析，并将该景观与实验确定的核小体结合偏好进行了比较。我们表明，具有增强的非特异性 TF-DNA 结合的 DNA 区域在统计学上显著缺乏核小体。因此，我们认为 TF 与组蛋白之间争夺非特异性结合基因组序列的竞争可能是影响体内核小体结合偏好的重要机制。我们还预测，聚（dA:dT）和聚（dC:dG）序列代表具有最强非特异性 TF-DNA 结合倾向的基因组元件，从而允许 TF 在这些元件上与核小体竞争。我们的结果表明，非特异性 TF-DNA 结合可能为核小体在整个酵母基因组中的统计定位提供了障碍。我们预测，该障碍的强度随着细胞中 DNA 结合蛋白浓度的增加而增加。我们讨论了所提出的机制与最近发现的活性核小体重建途径的联系。
