Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses
Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses
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DOI：
10.1186/gb-2007-8-6-r101
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发表时间：
2007-01-01
期刊：
影响因子：
12.3
通讯作者：
Halfon, Marc S.
中科院分区：
文献类型：
--
作者：
Li, Long;Zhu, Qianqian;Halfon, Marc S.
背景：转录顺式调控模块（如增强子）在调控基因表达中起着关键作用。虽然许多个别监管元件的特点，他们从来没有被分析为一个class.Results：我们已经进行了第一次这样大规模的研究，顺式调控模块，以确定他们是否有共同的属性，可能有助于他们的识别，并有助于我们理解的机制，它们的功能。共280个人，实验验证的顺式调节模块从果蝇进行了分析的序列水平和功能特性的范围。我们在这里报告说，调控模块确实有共同的特性，其中GC含量升高，种间序列保守性增加，并有被转录成RNA的趋势。然而，我们发现转录因子结合位点的密集聚类，特别是同型聚类，这通常被认为是调控模块的一般特征，而是主要属于特定亚类的特征。这对当前的计算方法有重要的影响，其中许多方法都偏向于这个子集。我们探讨了两种新的策略，以评估结合位点聚类和衡量他们的表现，他们的能力，以检测所有280个模块和各种功能一致的subsets.Conclusion：我们的研究结果表明，顺式调控模块共享的共同特点，有助于将它们定义为一类，并可能导致新的见解基因调控机制。然而，这些特性本身可能不足以可靠地区分调控序列和非调控序列。我们还表明，有不同的子类顺式调控模块，更适合在硅片检测比别人，这些差异必须考虑到当尝试全基因组调控元件的发现。
Background: Transcriptional cis-regulatory modules (for example, enhancers) play a critical role in regulating gene expression. While many individual regulatory elements have been characterized, they have never been analyzed as a class.Results: We have performed the first such large-scale study of cis-regulatory modules in order to determine whether they have common properties that might aid in their identification and contribute to our understanding of the mechanisms by which they function. A total of 280 individual, experimentally verified cis-regulatory modules from Drosophila were analyzed for a range of sequence-level and functional properties. We report here that regulatory modules do indeed share common properties, among them an elevated GC content, an increased level of interspecific sequence conservation, and a tendency to be transcribed into RNA. However, we find that dense clustering of transcription factor binding sites, especially homotypic clustering, which is commonly believed to be a general characteristic of regulatory modules, is rather a feature that belongs chiefly to a specific subclass. This has important implications for current computational approaches, many of which are biased toward this subset. We explore two new strategies to assess binding site clustering and gauge their performances with respect to their ability to detect all 280 modules and various functionally coherent subsets.Conclusion: Our findings demonstrate that cis-regulatory modules share common features that help to define them as a class and that may lead to new insights into mechanisms of gene regulation. However, these properties alone may not be sufficient to reliably distinguish regulatory from nonregulatory sequences. We also demonstrate that there are distinct subclasses of cis-regulatory modules that are more amenable to in silico detection than others and that these differences must be taken into account when attempting genome-wide regulatory element discovery.