title: The DNA-binding network of Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20-30 s. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA-binding network consists of ~16,000 binding events from 154 TFs. We identify >50 TF-DNA consensus motifs and >1,150 promoter-binding events directly associated with proximal gene regulation. An additional ~4,200 binding events are in promoter windows and represent strong candidates for direct transcriptional regulation under appropriate environmental conditions. However, we also identify >10,000 'dormant' DNA-binding events that cannot be linked directly with proximal transcriptional control, suggesting that widespread DNA binding may be a common feature that should be considered when developing global models of coordinated gene expression.
authors.affiliation: 1] Seattle Biomedical Research Institute, Seattle, Washington 98109, USA [2] Interdisciplinary Program of Pathobiology, Department of Global Health, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Minch
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
authors.forename: Tige R
authors.initials: TR
authors.lastname: Rustad
authors.affiliation: Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA.
authors.forename: Eliza J R
authors.initials: EJ
authors.lastname: Peterson
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Winkler
authors.affiliation: Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiss
authors.affiliation: 1] Seattle Biomedical Research Institute, Seattle, Washington 98109, USA [2] Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA [3] Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Ma
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hickey
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
authors.forename: William
authors.initials: W
authors.lastname: Brabant
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Morrison
authors.affiliation: Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA.
authors.forename: Serdar
authors.initials: S
authors.lastname: Turkarslan
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Mawhinney
authors.affiliation: 1] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA [2] Department of Microbiology, Boston University, Boston, Massachusetts 02215, USA [3] Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA [4] The Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Galagan
authors.affiliation: Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Price
authors.affiliation: Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, USA.
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
authors.affiliation: 1] Seattle Biomedical Research Institute, Seattle, Washington 98109, USA [2] Interdisciplinary Program of Pathobiology, Department of Global Health, University of Washington, Seattle, Washington 98195, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Sherman
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005822:Genetic Vectors; D055106:Genome-Wide Association Study; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000235:genetics; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012372:ROC Curve; D011994:Recombinant Proteins / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors