期刊
NATURE
卷 499, 期 7457, 页码 178-183出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12337
关键词
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资金
- National Institute of Allergy and Infectious Diseases National Institute of Health, Department of Health and Human Services [HHSN272200800059C, U19 AI 076217, R01 AI 071155]
- Paul G. Allen Family Foundation
- National Science Foundation Pre-doctoral Fellowship Program
- Burroughs Wellcome Fund Award for Translational Research
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.
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