Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, IL 60637, USA.
BMC Genomics. 2010 Oct 19;11:581. doi: 10.1186/1471-2164-11-581.
How the transcription factor binding sites (TFBSs) are distributed in the promoter region have implications for gene regulation. Previous studies used the translation start codon as the reference point to infer the TFBS distribution. However, it is biologically more relevant to use the transcription start site (TSS) as the reference point. In this study, we reexamined the spatial distribution of TFBSs, investigated various promoter features that may affect the distribution, and studied the effect of TFBS distribution on transcriptional regulation.
We found a sharp peak for the distribution of TFBSs at ~115 bp upstream of the TSS, but no clear peak when the translation start codon was used as the reference point. Our analysis of sequence variation data among 63 yeast strains revealed very low deletion polymorphisms in the region between the distribution peak and the TSS, suggesting that the distances between TFBSs and the TSS have been selectively constrained in evolution. As in previous studies, we found that the nucleosome occupancy and the presence/absence of TATA-box in the promoter region affect the TFBS distribution pattern. In addition, we found that there exists a correlation between the 5'UTR length and the TFBS distribution pattern and we showed that the TFBS distribution pattern affects gene transcription level and plasticity.
The spatial distribution of TFBSs obtained using the TSS as the reference point shows a much sharper peak than does the distribution obtained using the translation start codon as the reference point. The TFBS distribution pattern is affected by nucleosome occupancy and presence of TATA-box and it affects the transcription level and transcription plasticity of the gene.
转录因子结合位点（TFBS）在启动子区域中的分布方式对基因调控具有重要意义。先前的研究使用翻译起始密码子作为参考点来推断 TFBS 的分布。然而，使用转录起始位点（TSS）作为参考点在生物学上更为相关。在这项研究中，我们重新检查了 TFBS 的空间分布，研究了可能影响分布的各种启动子特征，并研究了 TFBS 分布对转录调控的影响。
我们发现 TFBS 在 TSS 上游约 115bp 处的分布有一个明显的峰值，但当使用翻译起始密码子作为参考点时，没有明显的峰值。我们对 63 株酵母菌株的序列变异数据进行分析，发现分布峰值和 TSS 之间的区域内非常低的缺失多态性，这表明 TFBS 和 TSS 之间的距离在进化过程中受到了选择性限制。与先前的研究一样，我们发现启动子区域中核小体占有率和 TATA 盒的存在/缺失会影响 TFBS 分布模式。此外，我们发现 5'UTR 长度与 TFBS 分布模式之间存在相关性，并且表明 TFBS 分布模式会影响基因转录水平和可塑性。
使用 TSS 作为参考点获得的 TFBS 空间分布比使用翻译起始密码子作为参考点获得的分布具有更明显的峰值。TFBS 分布模式受核小体占有率和 TATA 盒的存在影响，并且影响基因的转录水平和转录可塑性。
