Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
Nucleic Acids Res. 2013 Jun;41(11):5569-81. doi: 10.1093/nar/gkt256. Epub 2013 Apr 17.
The core promoter is the region in which RNA polymerase II is recruited to the DNA and acts to initiate transcription, but the extent to which the core promoter sequence determines promoter activity levels is largely unknown. Here, we identified several base content and k-mer sequence features of the yeast core promoter sequence that are highly predictive of maximal promoter activity. These features are mainly located in the region 75 bp upstream and 50 bp downstream of the main transcription start site, and their associations hold for both constitutively active promoters and promoters that are induced or repressed in specific conditions. Our results unravel several architectural features of yeast core promoters and suggest that the yeast core promoter sequence downstream of the TATA box (or of similar sequences involved in recruitment of the pre-initiation complex) is a major determinant of maximal promoter activity. We further show that human core promoters also contain features that are indicative of maximal promoter activity; thus, our results emphasize the important role of the core promoter sequence in transcriptional regulation.
核心启动子是 RNA 聚合酶 II 被招募到 DNA 并启动转录的区域,但核心启动子序列在多大程度上决定启动子活性水平在很大程度上是未知的。在这里,我们确定了酵母核心启动子序列中的几个碱基含量和 K-mer 序列特征,这些特征高度预测了最大启动子活性。这些特征主要位于主要转录起始位点上游 75bp 和下游 50bp 的区域,它们的关联适用于组成型活性启动子和在特定条件下诱导或抑制的启动子。我们的结果揭示了酵母核心启动子的几个结构特征,并表明 TATA 盒下游的酵母核心启动子序列(或参与募集起始前复合物的类似序列)是最大启动子活性的主要决定因素。我们进一步表明,人类核心启动子也包含指示最大启动子活性的特征;因此,我们的结果强调了核心启动子序列在转录调控中的重要作用。