Document Detail


Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses.
MedLine Citation:
PMID:  19729616     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ido Amit; Manuel Garber; Nicolas Chevrier; Ana Paula Leite; Yoni Donner; Thomas Eisenhaure; Mitchell Guttman; Jennifer K Grenier; Weibo Li; Or Zuk; Lisa A Schubert; Brian Birditt; Tal Shay; Alon Goren; Xiaolan Zhang; Zachary Smith; Raquel Deering; Rebecca C McDonald; Moran Cabili; Bradley E Bernstein; John L Rinn; Alex Meissner; David E Root; Nir Hacohen; Aviv Regev
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-03
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  326     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-09     Completed Date:  2009-10-19     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  257-63     Citation Subset:  IM    
Affiliation:
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE17721
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacteria / immunology*
Chromatin Assembly and Disassembly
DNA, Single-Stranded / immunology
Dendritic Cells / immunology*,  metabolism*
Feedback, Physiological
Gene Expression Profiling
Gene Expression Regulation*
Gene Regulatory Networks*
Inflammation / immunology,  metabolism*
Lipopeptides / immunology
Lipopolysaccharides / immunology
Mice
Mice, Inbred C57BL
Poly I-C / immunology
RNA-Binding Proteins / metabolism
Toll-Like Receptors / agonists
Transcription Factors / metabolism
Transcription, Genetic
Viruses / immunology*
Grant Support
ID/Acronym/Agency:
DP1 OD003958-01/OD/NIH HHS; DP1 OD003958-05/OD/NIH HHS; DP2 OD002230-01/OD/NIH HHS; R21 AI071060-01/AI/NIAID NIH HHS; R21 AI71060/AI/NIAID NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/DNA, Single-Stranded; 0/Lipopeptides; 0/Lipopolysaccharides; 0/Pam(3)CSK(4) peptide; 0/RNA-Binding Proteins; 0/Toll-Like Receptors; 0/Transcription Factors; 24939-03-5/Poly I-C
Comments/Corrections

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