小鼠锌指蛋白家族大脑调控网络构建.pdfVIP

7th OAPS Working Paper Series Paper No. 2010-0 17 Website: http://www.oaps.hk/ 小鼠锌指蛋白家族大脑调控网络构建 Construction of Mouse Zinc-finger Protein Regulatory Network in Brain 吴楚 Chu WU 生命科学与技术学院 School of Life Sciences and Biotechnology 摘要 背景：锌指蛋白是一类重要的调控网络转录因子家族，调控很多生物学过程，尤其是中枢神经 系统的发育。目前对锌指蛋白转录因子家族调控网络的报道还很少见。为了进一步了解小鼠大脑中 锌指蛋白转录因子的调控机制，我们采用了生物信息学方法对小鼠全基因组表达谱进行了分析。 结果：我们构建了一个包含17 个锌指蛋白和245 个靶基因的调控网络。调控网络根据其基因 组表达谱被进一步分成 11 个模块。对基本调控网络模体的分析也显示出网络的复杂性和多样性。 我们发现一个新的在Zinc1 和Zfp365 间发生的交互抑制，这种抑制过程广泛存在于各种脑组织， 并导致它们的功能分化。 结论：我们构建的调控网络是可信的。并且对于了解锌指蛋白转录因子在小鼠大脑发育过程中 起到的重要作用，提供了大量信息。为今后的进一步实验验证提供了总体框架。 关键词：锌指蛋白，调控网络，小鼠大脑，调控模式 ABSTRACT Background: The Zinc-Finger proteins are important components of the transcriptional regulatory network, controlling a variety of biological processes, especially the development of the central nervous system. Until now, reports describing the regulatory network of the Zinc-Finger transcription factor (TF) family have been scarce. In order to understand the regulatory mechanisms of Zinc-Finger TFs in mouse brain, we inferred their regulatory network from genome-wide gene expression profiles with the bioinformatics method. Results: A regulatory network comprising 17 important Zinc-Finger TFs and 245 target genes was constructed. The network was divided into 11 modules based on expression profiles. A regulatory motif search shows the complexity and diversity of the network. Interestingly, some TFs in the network regulate more than one module. A novel cross-repression between Zinc1 and Zfp365 was identified, which may control various functions in different brain r