Systematic functional characterization of cis-regulatory motifs in human core promoters
Systematic functional characterization of cis-regulatory motifs in human core promoters
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DOI：
10.1101/gr.6828808
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发表时间：
2008-03-01
期刊：
影响因子：
7
通讯作者：
Segal, Eran
中科院分区：
文献类型：
--
作者：
Sinha, Saurabh;Adler, Adam S.;Segal, Eran
大量参与转录调控的顺式调控基序已被确定，但其中许多功能的调控背景和生物过程是未知的。在这里，我们通过计算确定了由基序靶向的人类核心启动子集，并通过使用基于基因集的方法和多种生物数据来源系统地表征了它们的功能。我们发现，大多数图案的目标集包含具有相似功能的基因和在体内共调节的基因，从而表明由图案调节的生物过程和这种调节可能发生的条件。我们的分析还确定了许多基序，其目标集被预测为由一个共同的microRNA调节，这表明转录和转录后控制过程之间的连接。最后，我们预测新的作用，为非特征的图案在特定的生物过程和某些类型的人类癌症的调节，并通过实验验证四个这样的预测，表明四个非特征的图案在细胞周期进程中的调节作用。因此，我们的分析提供了一个具体的框架，揭示全基因组顺式调控基序的生物学功能。
A large number of cis-regulatory motifs involved in transcriptional control have been identified, but the regulatory context and biological processes in which many of them function are unknown. Here, we computationally identify the sets of human core promoters targeted by motifs, and systematically characterize their function by using a robust gene-set-based approach and diverse sources of biological data. We find that the target sets of most motifs contain both genes with similar function and genes that are coregulated in vivo, thereby suggesting both the biological process regulated by the motifs and the conditions in which this regulation may occur. Our analysis also identifies many motifs whose target sets are predicted to be regulated by a common microRNA, suggesting a connection between transcriptional and post-transcriptional control processes. Finally, we predict novel roles for uncharacterized motifs in the regulation of specific biological processes and certain types of human cancer, and experimentally validate four such predictions, suggesting regulatory roles for four uncharacterized motifs in cell cycle progression. Our analysis thus provides a concrete framework for uncovering the biological function of cis-regulatory motifs genome wide.