TY - JOUR
T1 - Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses
AU - Arnit, Ido
AU - Garber, Manuel
AU - Chevrier, Nicolas
AU - Leite, Ana Paula
AU - Donner, Yoni
AU - Eisenhaure, Thomas
AU - Guttman, Mitchell
AU - Grenier, Jennifer K.
AU - Li, Weibo
AU - Zuk, Or
AU - Schubert, Lisa A.
AU - Birditt, Brian
AU - Shay, Tal
AU - Goren, Alon
AU - Zhang, Xiaolan
AU - Smith, Zachary
AU - Deering, Raquel
AU - McDonald, Rebecca C.
AU - Cabili, Moran
AU - Bernstein, Bradley E.
AU - Rinn, John L.
AU - Meissner, Alex
AU - Root, David E.
AU - Hacohen, Nir Hacohen A.
AU - Regev, Aviv
PY - 2009/10/9
Y1 - 2009/10/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70349882120&partnerID=8YFLogxK
U2 - 10.1126/science.1179050
DO - 10.1126/science.1179050
M3 - Article
C2 - 19729616
AN - SCOPUS:70349882120
SN - 0036-8075
VL - 326
SP - 257
EP - 263
JO - Science
JF - Science
IS - 5950
ER -