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Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses 请发到lulu19890119@163.com 谢谢，我只要这一篇文章，别给我一期的杂志，谢谢 |
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HarveyWang
捐助贵宾 (知名作家)
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我们只有一整本的，很遗憾。。。 Published Online September 3, 2009 Science DOI: 10.1126/science.1179050 Science Express Index Research Articles Submitted on July 14, 2009 Accepted on August 26, 2009 Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses Ido Amit 1, Manuel Garber 2, Nicolas Chevrier 3, Ana Paula Leite 4, Yoni Donner 2, Thomas Eisenhaure 3, Mitchell Guttman 5, Jennifer K. Grenier 2, Weibo Li 3, Or Zuk 2, Lisa A. Schubert 6, Brian Birditt 6, Tal Shay 2, Alon Goren 2, Xiaolan Zhang 2, Zachary Smith 2, Raquel Deering 3, Rebecca C. McDonald 3, Moran Cabili 2, Bradley E. Bernstein 2, John L. Rinn 2, Alex Meissner 2, David E. Root 2, Nir Hacohen 7*, Aviv Regev 5 1 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129 USA.; Harvard Medical School, Boston, MA 02115, USA.; MIT, Department of Biology, Cambridge, MA 02142, USA. 2 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. 3 Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129 USA.; Harvard Medical School, Boston, MA 02115, USA. 4 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.; Computational and Systems Biology, MIT Cambridge, MA 02139, USA. 5 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.; MIT, Department of Biology, Cambridge, MA 02142, USA. 6 NanoString Technologies, 530 Fairview Ave. N, Suite 2000, Seattle, WA 98109, USA. 7 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129 USA.; Harvard Medical School, Boston, MA 02115, USA. * To whom correspondence should be addressed. Nir Hacohen , E-mail: nhacohen@partners.org These authors contributed equally to this work. These authors contributed equally to this work. 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 |
4楼2009-09-30 10:53:02
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