Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Genome Biol. 2011 Dec 21;12(12):R125. doi: 10.1186/gb-2011-12-12-r125.
Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding specificities of most Saccharomyces cerevisiae TFs, but a comprehensive evaluation of their data has been lacking.
We analyzed in vitro and in vivo TF-DNA binding data reported in previous large-scale studies to generate a comprehensive, curated resource of DNA binding specificity data for all characterized S. cerevisiae TFs. Our collection comprises DNA binding site motifs and comprehensive in vitro DNA binding specificity data for all possible 8-bp sequences. Investigation of the DNA binding specificities within the basic leucine zipper (bZIP) and VHT1 regulator (VHR) TF families revealed unexpected plasticity in TF-DNA recognition: intriguingly, the VHR TFs, newly characterized by protein binding microarrays in this study, recognize bZIP-like DNA motifs, while the bZIP TF Hac1 recognizes a motif highly similar to the canonical E-box motif of basic helix-loop-helix (bHLH) TFs. We identified several TFs with distinct primary and secondary motifs, which might be associated with different regulatory functions. Finally, integrated analysis of in vivo TF binding data with protein binding microarray data lends further support for indirect DNA binding in vivo by sequence-specific TFs.
The comprehensive data in this curated collection allow for more accurate analyses of regulatory TF-DNA interactions, in-depth structural studies of TF-DNA specificity determinants, and future experimental investigations of the TFs' predicted target genes and regulatory roles.
转录因子（TFs）通过与与其靶基因相关的顺式调控 DNA 元件相互作用，在调节基因表达中发挥核心作用。最近的调查研究了大多数酿酒酵母 TFs 的 DNA 结合特异性，但缺乏对其数据的全面评估。
我们分析了先前大规模研究中报道的体外和体内 TF-DNA 结合数据，为所有已鉴定的酿酒酵母 TFs 生成了一个全面的、经过精心整理的 DNA 结合特异性数据资源。我们的集合包括 DNA 结合位点基序和所有可能的 8 个碱基对序列的综合体外 DNA 结合特异性数据。对基本亮氨酸拉链（bZIP）和 VHT1 调节因子（VHR）TF 家族内的 DNA 结合特异性进行研究，揭示了 TF-DNA 识别的意外可塑性：有趣的是，VHR TFs 是本研究中通过蛋白质结合微阵列新鉴定的，识别 bZIP 样 DNA 基序，而 bZIP TF Hac1 识别与基本螺旋-环-螺旋（bHLH）TFs 的典型 E 盒基序高度相似的基序。我们确定了几个具有不同主要和次要基序的 TF，这可能与不同的调节功能有关。最后，体内 TF 结合数据与蛋白质结合微阵列数据的综合分析进一步支持了序列特异性 TF 在体内的间接 DNA 结合。
经过精心整理的这个综合性数据集合，使我们能够更准确地分析调控 TF-DNA 相互作用、深入研究 TF-DNA 特异性决定因素，并对 TFs 预测的靶基因和调控作用进行未来的实验研究。
