Genome-wide co-occurrence of promoter elements reveals a cis-regulatory cassette of rRNA transcription motifs in Saccharomyces cerevisiae
Genome-wide co-occurrence of promoter elements reveals a cis-regulatory cassette of rRNA transcription motifs in Saccharomyces cerevisiae
复制标题
DOI：
10.1101/gr.301202
复制
发表时间：
2002-11-01
期刊：
影响因子：
7
通讯作者：
Church, GM
中科院分区：
文献类型：
--
作者：
Sudarsanam, P;Pilpel, Y;Church, GM
组合调控是真核生物转录的一个重要特征。然而，只有有限数量的研究在全基因组水平上表征了这方面。我们进行了一项全基因组计算调查，以确定在酿酒葡萄球菌基因组中大量启动子中共同出现的顺式调控基序对。一对新的基序，mRRPE和PAC，在基因组中共同出现的频率最高，主要在参与rRNA转录和加工的基因的启动子中。在大多数启动子中，mRRPE比PAC更接近ATG，这两个基序表现出明显的位置和取向偏差。另外两个rrna相关的基序，mRRSE3和mRRSE10，也与mRRPE和PAC共同发生。mRRPE和PAC是表达谱的主要决定因素，而mRRSE3和mRRSE10调节这些模式。我们描述了一种新的计算方法来研究启动子元件物理位置的功能意义，该方法结合了基因组序列和微阵列数据的分析。将这种方法应用于包含四个rRNA基序的调控盒表明，这些元件的相对启动子位置对下游基因的表达模式有深远的影响。这些发现为这些新的基序提供了功能，并深入了解了它们调节基因表达的机制。本文介绍的方法对于分析更复杂的基因组中的转录调控特别有用。
Combinatorial regulation is an important feature of eukaryotic transcription. However, only a limited number of studies have characterized this aspect on a whole-genome level. We have conducted a genome-wide computational survey to identify cis-regulatory motif pairs that co-occur in a significantly high number of promoters in the S. cerevisiae genome. A pair of novel motifs, mRRPE and PAC, co-occur most highly in the genome, primarily in the promoters of genes involved in rRNA transcription and processing. The two motifs show significant positional and orientational bias with mRRPE being closer to the ATG than PAC in most promoters. Two additional rRNA-related motifs, mRRSE3 and mRRSE10, also co-occur with mRRPE and PAC. mRRPE and PAC are the primary determinants of expression profiles while mRRSE3 and mRRSE10 modulate these patterns. We describe a new computational approach for Studying the functional significance of the physical locations of promoter elements that combine analyses of genome sequence and microarray data. Applying this methodology to the regulatory cassette containing the four rRNA motifs demonstrates that the relative promoter locations of these elements have a profound effect on the expression patterns of the downstream genes. These findings provide a function for these novel motifs and insight into the mechanism by which they regulate gene expression. The methodology introduced here should prove particularly useful for analyzing transcriptional regulation in more complex genomes.