非特异性转录因子-DNA结合影响酵母核小体占有率
Nonspecific transcription factor-DNA binding influences nucleosome occupancy in yeast
摘要：
在全基因组水平上定量地了解核小体占据的调节原理是真核生物基因组学的核心问题。在这里，我们解决这个问题，使用芽殖酵母，酿酒酵母，作为模式生物。我们进行了全基因组范围的计算分析的非特异性转录因子（TF）-DNA结合自由能景观，并比较这种景观与实验确定的核小体结合偏好。我们发现，增强非特异性TF-DNA结合的DNA区域的核小体在统计学上显着耗尽。因此，我们认为，TF与组蛋白之间的竞争非特异性结合基因组序列可能是一个重要的机制，影响核小体结合的喜好在体内。我们还预测，聚（dA：dT）和聚（dC：dG）tracts代表基因组元素与非特异性TF-DNA结合的最强倾向，从而使TF在这些元素的竞争胜过核小体。我们的研究结果表明，非特异性TF-DNA结合可能提供了一个障碍，在整个酵母基因组的核小体的统计定位。我们预测，这种屏障的强度随着细胞中DNA结合蛋白的浓度而增加。我们讨论了最近发现的主动核小体重建途径的拟议机制的连接。
英文摘要：
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 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.
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