a systems approach to mapping transcriptional networks controlling surfactant homeostasis一个系统的方法来绘制转录网络控制表面活性剂体内平衡.pdfVIP
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a systems approach to mapping transcriptional networks controlling surfactant homeostasis一个系统的方法来绘制转录网络控制表面活性剂体内平衡
Xu et al. BMC Genomics 2010, 11:451
/1471-2164/11/451
RESEARCH ARTICLE Open Access
A systems approach to mapping transcriptional
networks controlling surfactant homeostasis
1,2* 2,3 1 4 1 2,3 1
Yan Xu , Minlu Zhang , Yanhua Wang , Pooja Kadambi , Vrushank Dave , Long J Lu , Jeffrey A Whitsett
Abstract
Background: Pulmonary surfactant is required for lung function at birth and throughout life. Lung lipid and
surfactant homeostasis requires regulation among multi-tiered processes, coordinating the synthesis of surfactant
proteins and lipids, their assembly, trafficking, and storage in type II cells of the lung. The mechanisms regulating
these interrelated processes are largely unknown.
Results: We integrated mRNA microarray data with array independent knowledge using Gene Ontology (GO)
similarity analysis, promoter motif searching, protein interaction and literature mining to elucidate genetic networks
regulating lipid related biological processes in lung. A Transcription factor (TF) - target gene (TG) similarity matrix
was generated by integrating data from different analytic methods. A scoring function was built to rank the likely
TF-TG pairs. Using this strategy, we identified and verified critical components of a transcriptional network directing
lipogenesis, lipid trafficking and surfactant homeostasis in the mouse lung.
Conclusions: Within the transcriptional network, SREBP, CEBPA, FOXA2, ETSF, GATA6 and IRF1 were identified as
regulatory hubs displaying high connectivity. SREBP, FOXA2 and CEBPA together form a common core regulatory
module that controls surfactant lipid homeostasis. The core module cooperates with other factors to regulate lipid
metabolism and trans
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