Gertz Jason, Riles Linda, Turnbaugh Peter, Ho Su-Wen, Cohen Barak A
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Genome Res. 2005 Aug;15(8):1145-52. doi: 10.1101/gr.3859605.
Completing the annotation of a genome sequence requires identifying the regulatory sequences that control gene expression. To identify these sequences, we developed an algorithm that searches for short, conserved sequence motifs in the genomes of related species. The method is effective in finding motifs de novo and for refining known regulatory motifs in Saccharomyces cerevisiae. We tested one novel motif prediction of the algorithm and found it to be the binding site of Stp2; it is significantly different from the previously predicted Stp2 binding site. We show that Stp2 physically interacts with this sequence motif, and that stp2 mutations affect the expression of genes associated with the motif. We demonstrate that the Stp2 binding site also interacts genetically with Stp1, a regulator of amino acid permease genes and, with Sfp1, a key regulator of cell growth. These results illuminate an important transcriptional circuit that regulates cell growth through external nutrient uptake.
完成基因组序列的注释需要识别控制基因表达的调控序列。为了识别这些序列，我们开发了一种算法，该算法在相关物种的基因组中搜索短的、保守的序列基序。该方法在从头寻找基序以及完善酿酒酵母中已知的调控基序方面是有效的。我们测试了该算法的一个新的基序预测，发现它是Stp2的结合位点；它与先前预测的Stp2结合位点有显著差异。我们表明，Stp2与该序列基序发生物理相互作用，并且stp2突变会影响与该基序相关的基因的表达。我们证明，Stp2结合位点还与氨基酸通透酶基因的调节因子Stp1以及细胞生长的关键调节因子Sfp1发生遗传相互作用。这些结果揭示了一个重要的转录回路，该回路通过外部营养物质摄取来调节细胞生长。
