| Literature DB >> 23823726 |
James E Galagan1, Kyle Minch, Matthew Peterson, Anna Lyubetskaya, Elham Azizi, Linsday Sweet, Antonio Gomes, Tige Rustad, Gregory Dolganov, Irina Glotova, Thomas Abeel, Chris Mahwinney, Adam D Kennedy, René Allard, William Brabant, Andrew Krueger, Suma Jaini, Brent Honda, Wen-Han Yu, Mark J Hickey, Jeremy Zucker, Christopher Garay, Brian Weiner, Peter Sisk, Christian Stolte, Jessica K Winkler, Yves Van de Peer, Paul Iazzetti, Diogo Camacho, Jonathan Dreyfuss, Yang Liu, Anca Dorhoi, Hans-Joachim Mollenkopf, Paul Drogaris, Julie Lamontagne, Yiyong Zhou, Julie Piquenot, Sang Tae Park, Sahadevan Raman, Stefan H E Kaufmann, Robert P Mohney, Daniel Chelsky, D Branch Moody, David R Sherman, Gary K Schoolnik.
Abstract
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.Entities:
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Year: 2013 PMID： 23823726 PMCID： PMC4087036 DOI： 10.1038/nature12337
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962