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    Transcription Factor Activity Mapping of a Tissue-Specific Gene Regulatory Network

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    Authors
    MacNeil, Lesley T.
    Pons, Carles
    Arda, H. Efsun
    Giese, Gabrielle E.
    Myers, Chad L.
    Walhout, Albertha J. M.
    UMass Chan Affiliations
    Program in Molecular Medicine
    Program in Systems Biology
    Document Type
    Journal Article
    Publication Date
    2015-08-26
    Keywords
    Genetics and Genomics
    Systems Biology
    
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    Link to Full Text
    http://dx.doi.org/10.1016/j.cels.2015.08.003
    Abstract
    A wealth of physical interaction data between transcription factors (TFs) and DNA has been generated, but these interactions often do not have apparent regulatory consequences. Thus, equating physical interaction data with gene regulatory networks (GRNs) is problematic. Here, we comprehensively assay TF activity, rather than binding, to construct a network of gene regulatory interactions in the C. elegans intestine. By manually observing the in vivo tissue-specific knockdown of 921 TFs on a panel of 19 fluorescent transcriptional reporters, we identified a GRN of 411 interactions between 19 promoters and 177 TFs. This GRN shows only modest overlap with physical interactions, indicating that many regulatory interactions are indirect. We applied nested effects modeling to uncover information flow between TFs in the intestine that converges on a small set of physical TF-promoter interactions. We found numerous cell nonautonomous regulatory interactions, illustrating tissue-to-tissue communication. Altogether, our study illuminates the complexity of gene regulation in the context of a living animal.
    Source
    Cell Syst. 2015 Aug 26;1(2):152-162. Link to article on publisher's site
    DOI
    10.1016/j.cels.2015.08.003
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49958
    PubMed ID
    26430702
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cels.2015.08.003
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