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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
The Mycobacterium tuberculosis regulatory network and hypoxia
Nature, Volume 499, No. 7457, Year 2013
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Description
We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub. © 2013 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Galagan, James E.
United States, Boston
Boston University
United States, Cambridge
Massachusetts Institute of Technology
Minch, Kyle J.
United States, Seattle
Seattle Biomedical Research Institute
Rustad, Tige R.
United States, Seattle
Seattle Biomedical Research Institute
Dolganov, Gregory M.
United States, Stanford
Stanford University School of Medicine
Abeel, Thomas
United States, Cambridge
Massachusetts Institute of Technology
Belgium, Ghent
Universiteit Gent
Allard, René
Canada, Montreal
Institut de Recherche en Immunologie et en Cancérologie de L’université de Montréal
Yu, Wenhan
United States, Boston
Boston University
Hickey, Mark J.
United States, Seattle
Seattle Biomedical Research Institute
Weiner, Brian K.
United States, Cambridge
Massachusetts Institute of Technology
Sisk, Peter
United States, Cambridge
Massachusetts Institute of Technology
Stolte, Christian
United States, Cambridge
Massachusetts Institute of Technology
Van de Peer, Y.
Belgium, Ghent
Universiteit Gent
Dorhoi, Anca
Germany, Berlin
Max Planck Institute for Infection Biology
Mollenkopf, Hans Joachim
Germany, Berlin
Max Planck Institute for Infection Biology
Zhou, Yiyong
Canada, Montreal
Institut de Recherche en Immunologie et en Cancérologie de L’université de Montréal
Kaufmann, Stefan Hugo Ernst
Germany, Berlin
Max Planck Institute for Infection Biology
Mohney, Robert P.
United States, Morrisville
Metabolon, Inc.
Moody, David Branch
United States, Boston
Harvard Medical School
Sherman, David R.
United States, Seattle
Seattle Biomedical Research Institute
United States, Seattle
University of Washington
Schoolnik, Gary K.
United States, Stanford
Stanford University School of Medicine
Statistics
Citations: 395
Authors: 20
Affiliations: 10
Identifiers
Doi:
10.1038/nature12337
ISSN:
14764687
Research Areas
Genetics And Genomics
Noncommunicable Diseases