The Mycobacterium tuberculosis regulatory network and hypoxia.
Nature
; 499(7457): 178-83, 2013 Jul 11.
Article
en En
| MEDLINE
| ID: mdl-23823726
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_tuberculosis
Asunto principal:
Redes y Vías Metabólicas
/
Redes Reguladoras de Genes
/
Hipoxia
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nature
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos