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Nature. 2013 Jul 11;499(7457):178-83. doi: 10.1038/nature12337. Epub 2013 Jul 3.

The Mycobacterium tuberculosis regulatory network and hypoxia.

Author information

1
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA. jgalag@bu.edu

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.

PMID:
23823726
PMCID:
PMC4087036
DOI:
10.1038/nature12337
[Indexed for MEDLINE]
Free PMC Article

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