van Helden J, Rios A F, Collado-Vides J
Unité de Conformation des Macromolécules Biologiques, Université Libre de Bruxelles, CP 160/16, 50 av. F. D. Roosevelt, B-1050 Bruxelles, Belgium.
Nucleic Acids Res. 2000 Apr 15;28(8):1808-18. doi: 10.1093/nar/28.8.1808.
The application of microarray and related technologies is currently generating a systematic catalog of the transcriptional response of any single gene to a multiplicity of experimental conditions. Clustering genes according to the similarity of their transcriptional response provides a direct hint to the regulons of the different transcription factors, many of which have still not been characterized. We have developed a new method for deciphering the mechanism underlying the common transcriptional response of a set of genes, i.e. discovering cis -acting regulatory elements from a set of unaligned upstream sequences. This method, called dyad analysis, is based on the observation that many regulatory sites consist of a pair of highly conserved trinucleotides, spaced by a non-conserved region of fixed width. The approach is to count the number of occurrences of each possible spaced pair of trinucleotides, and to assess its statistical significance. The method is highly efficient in the detection of sites bound by C(6)Zn(2)binuclear cluster proteins, as well as other transcription factors. In addition, we show that the dyad and single-word analyses are efficient for the detection of regulatory patterns in gene clusters from DNA chip experiments. In combination, these programs should provide a fast and efficient way to discover new regulatory sites for as yet unknown transcription factors.
微阵列及相关技术的应用目前正在生成任何单个基因对多种实验条件的转录反应的系统目录。根据基因转录反应的相似性对基因进行聚类，可直接提示不同转录因子的调控子，其中许多转录因子尚未得到表征。我们开发了一种新方法来解读一组基因共同转录反应背后的机制，即从未对齐的上游序列集中发现顺式作用调控元件。这种方法称为二元分析，其基于这样的观察结果：许多调控位点由一对高度保守的三核苷酸组成，中间间隔一个固定宽度的非保守区域。该方法是计算每种可能的间隔三核苷酸对的出现次数，并评估其统计学意义。该方法在检测由C(6)Zn(2)双核簇蛋白以及其他转录因子结合的位点方面非常高效。此外，我们表明二元分析和单字分析对于从DNA芯片实验中检测基因簇中的调控模式很有效。综合起来，这些程序应该为发现尚未知转录因子的新调控位点提供一种快速有效的方法。
