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青年学者研究奖演讲。转录调控网络的结构、进化和动态。

Early Career Research Award Lecture. Structure, evolution and dynamics of transcriptional regulatory networks.

机构信息

MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

出版信息

Biochem Soc Trans. 2010 Oct;38(5):1155-78. doi: 10.1042/BST0381155.

DOI:10.1042/BST0381155
PMID:20863280
Abstract

The availability of entire genome sequences and the wealth of literature on gene regulation have enabled researchers to model an organism's transcriptional regulation system in the form of a network. In such a network, TFs (transcription factors) and TGs (target genes) are represented as nodes and regulatory interactions between TFs and TGs are represented as directed links. In the present review, I address the following topics pertaining to transcriptional regulatory networks. (i) Structure and organization: first, I introduce the concept of networks and discuss our understanding of the structure and organization of transcriptional networks. (ii) Evolution: I then describe the different mechanisms and forces that influence network evolution and shape network structure. (iii) Dynamics: I discuss studies that have integrated information on dynamics such as mRNA abundance or half-life, with data on transcriptional network in order to elucidate general principles of regulatory network dynamics. In particular, I discuss how cell-to-cell variability in the expression level of TFs could permit differential utilization of the same underlying network by distinct members of a genetically identical cell population. Finally, I conclude by discussing open questions for future research and highlighting the implications for evolution, development, disease and applications such as genetic engineering.

摘要

全基因组序列的可用性和丰富的基因调控文献使研究人员能够以网络的形式对生物体的转录调控系统进行建模。在这样的网络中,TFs(转录因子)和 TGs(靶基因)被表示为节点,TFs 和 TGs 之间的调控相互作用被表示为有向链接。在本综述中,我将讨论与转录调控网络相关的以下主题。(i)结构和组织:首先,我介绍网络的概念,并讨论我们对转录网络结构和组织的理解。(ii)进化:然后,我描述影响网络进化并塑造网络结构的不同机制和力量。(iii)动态:我讨论了将 mRNA 丰度或半衰期等动态信息与转录网络数据整合起来,以阐明调控网络动态的一般原理的研究。特别是,我讨论了 TF 表达水平的细胞间变异性如何允许遗传上相同的细胞群体的不同成员对同一潜在网络进行不同的利用。最后,我通过讨论未来研究的开放性问题并强调其对进化、发育、疾病和遗传工程等应用的影响来结束讨论。

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