Evolutionary analysis of regulatory sequences (EARS) in plants
Evolutionary analysis of regulatory sequences (EARS) in plants
复制标题
DOI：
10.1111/j.1365-313x.2010.04314.x
复制
发表时间：
2010-10-01
期刊：
影响因子：
7.2
通讯作者：
Ott, Sascha
中科院分区：
文献类型：
--
作者：
Picot, Emma;Krusche, Peter;Ott, Sascha
在DNA非编码区域内识别调控序列是阐明基因网络的关键步骤。然而，这种方法面临重大挑战，因为据认为只有极小部分的非编码DNA对基因调控有贡献。传统上，调控区域的定位涉及费力地构建启动子缺失系列，然后将其与报告基因融合，并在转基因生物中进行检测。生物信息学方法可用于扫描序列以寻找与已知调控基序的匹配，但目前这些方法因这类基序数量相对较少以及假阳性率较高而受阻。在此，我们展示了一种稳健且高度灵敏的计算机模拟方法，用于识别非编码DNA内的进化保守区域。这些区域内的序列保守性被视为对抗突变的进化压力的证据，这暗示了其功能重要性。我们在一小套特征明确的启动子上测试了该方法，并表明它能成功识别已知的调控区域。我们还表明，这些进化保守序列包含转录结合位点簇，通常被描述为调控模块。一个针对植物启动子分析进行优化的工具版本可在http://wsbc.warwick.ac.uk/ears/main.php在线获取。
P>Identification of regulatory sequences within non-coding regions of DNA is an essential step towards elucidation of gene networks. This approach constitutes a major challenge, however, as only a very small fraction of non-coding DNA is thought to contribute to gene regulation. The mapping of regulatory regions traditionally involves the laborious construction of promoter deletion series which are then fused to reporter genes and assayed in transgenic organisms. Bioinformatic methods can be used to scan sequences for matches for known regulatory motifs, however these methods are currently hampered by the relatively small amount of such motifs and by a high false-discovery rate. Here, we demonstrate a robust and highly sensitive, in silico method to identify evolutionarily conserved regions within non-coding DNA. Sequence conservation within these regions is taken as evidence for evolutionary pressure against mutations, which is suggestive of functional importance. We test this method on a small set of well characterised promoters, and show that it successfully identifies known regulatory regions. We further show that these evolutionarily conserved sequences contain clusters of transcription binding sites, often described as regulatory modules. A version of the tool optimised for the analysis of plant promoters is available online at http://wsbc.warwick.ac.uk/ears/main.php.