The architecture of the gene regulatory networks of different tissues.
The architecture of the gene regulatory networks of different tissues.
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DOI：
10.1093/bioinformatics/bts387
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发表时间：
2012-09-15
期刊：
影响因子：
--
通讯作者：
Wingender E
中科院分区：
文献类型：
--
作者：
Li J;Hua X;Haubrock M;Wang J;Wingender E
摘要：人类细胞类型在形态和功能上的巨大多样性是由于不同细胞类型中不同的基因表达谱受不同的调控网络所控制。解释调控网络如何实现不同细胞类型的多样性仍然是一个具有挑战性的任务。在这里，我们通过构建八种人体组织的调节网络，包括转录因子（tf）、microRNAs （miRNAs）和非tf靶基因之间的调节相互作用，报告了我们对组织调节系统设计原则的研究。结果表明，组织网络中存在高进/出度的进/出中心。一些集线器（强集线器）在它们表达的所有组织中保持集线器状态，而另一些集线器（弱集线器）尽管无处不在地表达，但仅在某些组织中是集线器。网络基序主要是前馈回路。其中一些不含mirna的是所有组织共有的基序，而其他含有mirna的则是一个或几个组织拥有的组织特异性基序，这表明转录调控在组织间比转录后调控更为保守。特别地，一个共同的领结框架被发现是基序实例的基础，并在不同的组织中显示出不同的模式。这种“领结”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变异性，可以作为进一步了解调控系统对不同细胞功能特定要求的结构适应性的模型。联系人:edgar.wingender@bioinf.med.uni-goettingen.de;jwang@nju.edu.cn补充信息：补充数据可在Bioinformatics网站在线获得。
Summary: 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. Contact: edgar.wingender@bioinf.med.uni-goettingen.de; jwang@nju.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.
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影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
影响因子：
4.4
作者：
Linsen SE;de Wit E;de Bruijn E;Cuppen E
通讯作者：
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影响因子：
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作者：
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Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
DOI：
10.1126/science.1175202
发表时间：
2009-07-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Swirski FK;Nahrendorf M;Etzrodt M;Wildgruber M;Cortez-Retamozo V;Panizzi P;Figueiredo JL;Kohler RH;Chudnovskiy A;Waterman P;Aikawa E;Mempel TR;Libby P;Weissleder R;Pittet MJ
通讯作者：
Pittet MJ