Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses.
Ido Amit,Manuel Garber,Nicolas Chevrier,Ana Paula Leite,Ana Paula Leite,Yoni Donner,Thomas Eisenhaure,Mitchell Guttman,Mitchell Guttman,Jennifer K. Grenier,Weibo Li,Or Zuk,Lisa A. Schubert,Brian Birditt,Tal Shay,Alon Goren,Alon Goren,Xiaolan Zhang,Zachary D. Smith,Raquel P. Deering,Rebecca C. McDonald,Moran N. Cabili,Bradley E. Bernstein,Bradley E. Bernstein,John L. Rinn,Alexander Meissner,David E. Root,Nir Hacohen,Nir Hacohen,Aviv Regev,Aviv Regev,Aviv Regev +31 more
TLDR
This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells.Abstract:
Models of mammalian regulatory networks controlling gene expression have been inferred from genomic data but have largely not been validated. We present an unbiased strategy to systematically perturb candidate regulators and monitor cellular transcriptional responses. We applied this approach to derive regulatory networks that control the transcriptional response of mouse primary dendritic cells to pathogens. Our approach revealed the regulatory functions of 125 transcription factors, chromatin modifiers, and RNA binding proteins, which enabled the construction of a network model consisting of 24 core regulators and 76 fine-tuners that help to explain how pathogen-sensing pathways achieve specificity. This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells.read more
Citations
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Genetics and pathogenesis of inflammatory bowel disease
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RNA sequencing: advances, challenges and opportunities
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References
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Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data
Eran Segal,Michael Y. Shapira,Aviv Regev,Aviv Regev,Dana Pe'er,David Botstein,Daphne Koller,Nir Friedman +7 more
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