Bioinformatics and Genomics program, Center for Genomic Regulation and Pompeu Fabra University, Barcelona, Spain.
PLoS One. 2011;6(9):e24279. doi: 10.1371/journal.pone.0024279. Epub 2011 Sep 9.
The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of 6 'proximal promoter motifs' (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.
酵母转录因子的序列特异性及其结合位点预测的比较基因组算法的可用性,使得全面注释转录因子结合位点成为可能。在此,我们使用这种全基因组注释来全面研究酵母启动子的结构,重点研究转录因子结合位点相对于转录起始位点的分布,以及 TATA 和无 TATA 启动子的结构。对于大多数转录因子来说,结合位点在 TATA 启动子中的位置更上游,并且分布范围更广;而在无 TATA 启动子中,结合位点的位置则更靠近转录起始位点。相比之下,一组 6 个“近端启动子基序”(GAT1/GLN3/DAL80、FKH1/2、PBF1/2、RPN4、NDT80 和 ROX1)优先出现在无 TATA 启动子中,并且在这些启动子中强烈倾向于靠近转录起始位点结合。我们提供的证据表明,起始前复合物在 TATA 启动子中的 TATA 位点和无 TATA 启动子中其他近端启动子基序的位点被招募。无 TATA 启动子通常可以根据它们所包含的近端启动子基序进行分类,不同类别的无 TATA 启动子显示出不同的转录因子结合位点定位和核小体覆盖模式。这些观察结果表明,不同的转录起始调控模式可能在不同的启动子类别中发挥作用。此外,我们还表明,在所有启动子类别中,无核小体区域与转录因子结合位点密度最高的区域之间存在紧密匹配。转录因子结合位点密度与核小体缺失之间的紧密一致性表明,转录因子和核小体之间存在直接且普遍的竞争,以结合启动子。