Unbiased Reconstruction of a Mammalian Transcriptional Network
Mediating Pathogen Responses.
Amit I, Garber M, Chevrier N, Leite AP, Donner Y, Eisenhaure T, Guttman
M, Grenier JK, Li W, Zuk O, Schubert LA, Birditt B, Shay T, Goren A,
Zhang X, Smith Z, Deering R, McDonald RC, Cabili M, Bernstein BE, Rinn
JL, Meissner A, Root DE, Hacohen N, Regev A.
Science. 2009 Sep 3.
Models of mammalian regulatory networks controlling gene expression
have been inferred from genomic data, yet have largely not been
validated. We present an unbiased strategy to systematically perturb
candidate regulators and monitor cellular transcriptional responses. We
apply this approach to derive regulatory networks that control the
transcriptional response of mouse primary dendritic cells (DCs) to
pathogens. Our approach revealed the regulatory functions of 125
transcription factors, chromatin modifiers, and RNA binding proteins
and constructed a network model consisting of two dozen core regulators
and 76 fine-tuners that help 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.
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Klaas Vandepoele, PhD
Tel. 32 (0)9 33 13822
VIB Department of Plant Systems Biology, Ghent University
Technologiepark 927, 9052 Gent, Belgium
E-mail: Klaas.Vandepoele@psb.vib-ugent.be
Website: http://bioinformatics.psb.ugent.be/
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