title: Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis.
abstract: Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics.
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey 07103, USA.
authors.forename: Rinki
authors.initials: R
authors.lastname: Chauhan
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey 07103, USA.
authors.forename: Janani
authors.initials: J
authors.lastname: Ravi
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey 07103, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Datta
authors.affiliation: Department of Physics, University of Houston, Houston, Texas 77204-5005, USA.|Texas Center for Superconductivity, University of Houston, Houston, Texas 77204-5002, USA.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10021, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schnappinger
authors.affiliation: Department of Physics, University of Houston, Houston, Texas 77204-5005, USA.|Texas Center for Superconductivity, University of Houston, Houston, Texas 77204-5002, USA.|Max-Planck-Institut für Physik komplexer Systeme, Nöthnitzer Strasse 38, D-01187 Dresden, Germany.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bassler
authors.affiliation: Laufer Center for Physical &Quantitative Biology and Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Gábor
authors.initials: G
authors.lastname: Balázsi
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey 07103, USA.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Gennaro
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor