Signal transducers and activators of transcription-1 (STAT1) regulates microRNA transcription in interferon gamma-stimulated HeLa cells.
Signal transducers and activators of transcription-1 (STAT1) regulates microRNA transcription in interferon gamma-stimulated HeLa cells.
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DOI：
10.1371/journal.pone.0011794
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发表时间：
2010-07-26
期刊：
影响因子：
3.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Wang G;Wang Y;Teng M;Zhang D;Li L;Liu Y
基因调控网络的构建和建模是系统生物学的中心主题之一。随着对microRNA生物合成机制及其生物学功能的深入了解，建立microRNA介导的基因调控网络不仅是理想的，而且是可以实现的。在这项研究中，我们提出了一种生物信息学策略，使用转录因子和RNA聚合酶II（RPol II）的全基因组结合模式构建microRNA介导的调控网络，该模式使用染色质免疫沉淀下一代测序（ChIP-seq）技术获得。我们的策略包括三个关键步骤，使用RPol II结合模式鉴定初级microRNA转录物的转录起始位点和启动子区域，选择与ChIP-seq检测靶向的转录因子协同作用的协同转录因子，以及构建包含转录因子和microRNA的调控级联的网络。使用CAMDA（海量数据分析的关键评估）2009数据集，包括在对照条件下和干扰素γ刺激下HeLa S3细胞中RPol II和STAT 1（信号转导和转录激活因子1）的ChIP-seq数据，我们首先鉴定了HeLa细胞中83种microRNA的启动子区域。然后，我们确定了两个潜在的STAT 1协作因子，AP-1和C/EBP（CCAAT增强子结合蛋白），并进一步建立了8个反馈网络元件，这些元件可能在干扰素γ刺激期间调节细胞反应。这项研究提供了一种生物信息学策略，根据来自ChIP-seq实验的全基因组蛋白质-DNA相互作用数据，为microRNA介导的转录调控机制提供可检验的假设。
Constructing and modeling the gene regulatory network is one of the central themes of systems biology. With the growing understanding of the mechanism of microRNA biogenesis and its biological function, establishing a microRNA-mediated gene regulatory network is not only desirable but also achievable. In this study, we propose a bioinformatics strategy to construct the microRNA-mediated regulatory network using genome-wide binding patterns of transcription factor(s) and RNA polymerase II (RPol II), derived using chromatin immunoprecipitation following next generation sequencing (ChIP-seq) technology. Our strategy includes three key steps, identification of transcription start sites and promoter regions of primary microRNA transcripts using RPol II binding patterns, selection of cooperating transcription factors that collaboratively function with the transcription factors targeted by ChIP-seq assay, and construction of the network that contains regulatory cascades of both transcription factors and microRNAs. Using CAMDA (Critical Assessment of Massive Data Analysis) 2009 data set that includes ChIP-seq data on RPol II and STAT1 (signal transducers and activators of transcription 1) in HeLa S3 cells in control condition and with interferon γ stimulation, we first identified promoter regions of 83 microRNAs in HeLa cells. We then identified two potential STAT1 collaborating factors, AP-1 and C/EBP (CCAAT enhancer-binding proteins), and further established eight feedback network elements that may regulate cellular response during interferon γ stimulation. This study offers a bioinformatics strategy to provide testable hypotheses on the mechanisms of microRNA-mediated transcriptional regulation, based upon genome-wide protein-DNA interaction data derived from ChIP-seq experiments.
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