Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses

被引:58
|
作者
Li, Long
Zhu, Qianqian
He, Xin
Sinha, Saurabh
Halfon, Marc S. [1 ]
机构
[1] SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA
[2] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14214 USA
[3] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA
[4] New York State Ctr Excellence Bioinformat & Life, Buffalo, NY 14203 USA
[5] Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA
关键词
D O I
10.1186/gb-2007-8-6-r101
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
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页数:16
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