Scientific Publications

The Mycobacterium tuberculosis regulatory network and hypoxia.

Publication TypeJournal Article
AuthorsGalagan, JE, Minch K., Peterson M., Lyubetskaya A., Azizi E., Sweet L., Gomes A., Rustad T., Dolganov G., Glotova I., Abeel T., Mahwinney C., Kennedy AD, Allard R., Brabant W., Krueger A., Jaini S., Honda B., Yu WH, Hickey MJ, Zucker J., Garay C., Weiner B., Sisk P., Stolte C., Winkler JK, Van de Peer Y., Iazzetti P., Camacho D., Dreyfuss J., Liu Y., Dorhoi A., Mollenkopf HJ, Drogaris P., Lamontagne J., Zhou Y., Piquenot J., Park ST, Raman S., Kaufmann SH, Mohney RP, Chelsky D., Moody DB, Sherman DR, and Schoolnik GK
AbstractWe 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.
Year of Publication2013
JournalNature
Volume499
Issue7457
Pages178-183
Date Published (YYYY/MM/DD)2013/07/11
ISSN Number0028-0836
DOI10.1038/nature12337
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23823726?dopt=Abstract