Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA.
Trends Genet. 2010 Feb;26(2):75-83. doi: 10.1016/j.tig.2009.12.003. Epub 2010 Jan 13.
The initiation of transcription is regulated by transcription factors (TFs) binding to DNA response elements (REs). How do TFs recognize specific binding sites among the many similar ones available in the genome? Recent research has illustrated that even a single nucleotide substitution can alter the selective binding of TFs to coregulators, that prior binding events can lead to selective DNA binding, and that selectivity is influenced by the availability of binding sites in the genome. Here, we combine structural insights with recent genomics screens to address the problem of TF-DNA interaction specificity. The emerging picture of selective binding site sequence recognition and TF activation involves three major factors: the cellular network, protein and DNA as dynamic conformational ensembles and the tight packing of multiple TFs and coregulators on stretches of regulatory DNA. The classification of TF recognition mechanisms based on these factors impacts our understanding of how transcription initiation is regulated.
转录的起始受转录因子（TFs）与 DNA 反应元件（REs）结合的调控。TFs 如何在基因组中众多相似的结合位点中识别特定的结合位点？最近的研究表明，即使单个核苷酸的替换也可以改变 TFs 与共激活因子的选择性结合，先前的结合事件可以导致选择性 DNA 结合，并且选择性受基因组中结合位点的可用性影响。在这里，我们将结构见解与最近的基因组学筛选相结合，以解决 TF-DNA 相互作用特异性的问题。选择性结合位点序列识别和 TF 激活的新兴图景涉及三个主要因素：细胞网络、作为动态构象集合的蛋白质和 DNA 以及多个 TF 和共激活因子在调节 DNA 片段上的紧密包装。基于这些因素对 TF 识别机制的分类影响了我们对转录起始如何受到调控的理解。
