The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Göttingen, Germany.
Bioinformatics. 2012 Sep 15;28(18):i509-i514. doi: 10.1093/bioinformatics/bts387.
The great variety of human cell types in morphology and function is due to the diverse gene expression profiles that are governed by the distinctive regulatory networks in different cell types. It is still a challenging task to explain how the regulatory networks achieve the diversity of different cell types. Here, we report on our studies of the design principles of the tissue regulatory system by constructing the regulatory networks of eight human tissues, which subsume the regulatory interactions between transcription factors (TFs), microRNAs (miRNAs) and non-TF target genes. The results show that there are in-/out-hubs of high in-/out-degrees in tissue networks. Some hubs (strong hubs) maintain the hub status in all the tissues where they are expressed, whereas others (weak hubs), in spite of their ubiquitous expression, are hubs only in some tissues. The network motifs are mostly feed-forward loops. Some of them having no miRNAs are the common motifs shared by all tissues, whereas the others containing miRNAs are the tissue-specific ones owned by one or several tissues, indicating that the transcriptional regulation is more conserved across tissues than the post-transcriptional regulation. In particular, a common bow-tie framework was found that underlies the motif instances and shows diverse patterns in different tissues. Such bow-tie framework reflects the utilization efficiency of the regulatory system as well as its high variability in different tissues, and could serve as the model to further understand the structural adaptation of the regulatory system to the specific requirements of different cell functions.
edgar.wingender@bioinf.med.uni-goettingen.de; jwang@nju.edu.cn
Supplementary data are available at Bioinformatics online.
人类细胞在形态和功能上的多样性是由于不同细胞类型中独特的调控网络所控制的基因表达谱的多样化。解释调控网络如何实现不同细胞类型的多样性仍然是一项具有挑战性的任务。在这里，我们通过构建八个人类组织的调控网络，报告了我们对组织调控系统设计原理的研究，该网络包含了转录因子（TFs）、microRNAs（miRNAs）和非 TF 靶基因之间的调控相互作用。结果表明，组织网络中存在高输入/输出度的输入/输出枢纽。一些枢纽（强枢纽）在其表达的所有组织中保持枢纽状态，而另一些枢纽（弱枢纽）尽管广泛表达，但只是在一些组织中是枢纽。网络基元主要是前馈环。其中一些没有 miRNA 的是所有组织共有的常见基元，而另一些含有 miRNA 的则是一个或几个组织特有的基元，这表明转录调控比转录后调控在组织间更保守。特别是，发现了一个常见的蝴蝶结框架，它是基元实例的基础，并在不同的组织中表现出不同的模式。这种蝴蝶结框架反映了调控系统的利用效率及其在不同组织中的高度可变性，可以作为进一步理解调控系统对不同细胞功能特定要求的结构适应的模型。
edgar.wingender@bioinf.med.uni-goettingen.de; jwang@nju.edu.cn
补充数据可在“生物信息学”在线获取。
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