title: Identification of regulatory network topological units coordinating the genome-wide transcriptional response to glucose in Escherichia coli.
abstract: BACKGROUND
  Glucose is the preferred carbon and energy source for Escherichia coli. A complex regulatory network coordinates gene expression, transport and enzyme activities in response to the presence of this sugar. To determine the extent of the cellular response to glucose, we applied an approach combining global transcriptome and regulatory network analyses.
  
  
  RESULTS
  Transcriptome data from isogenic wild type and crp- strains grown in Luria-Bertani medium (LB) or LB + 4 g/L glucose (LB+G) were analyzed to identify differentially transcribed genes. We detected 180 and 200 genes displaying increased and reduced relative transcript levels in the presence of glucose, respectively. The observed expression pattern in LB was consistent with a gluconeogenic metabolic state including active transport and interconversion of small molecules and macromolecules, induction of protease-encoding genes and a partial heat shock response. In LB+G, catabolic repression was detected for transport and metabolic interconversion activities. We also detected an increased capacity for de novo synthesis of nucleotides, amino acids and proteins. Cluster analysis of a subset of genes revealed that CRP mediates catabolite repression for most of the genes displaying reduced transcript levels in LB+G, whereas Fis participates in the upregulation of genes under this condition. An analysis of the regulatory network, in terms of topological functional units, revealed 8 interconnected modules which again exposed the importance of Fis and CRP as directly responsible for the coordinated response of the cell. This effect was also seen with other not extensively connected transcription factors such as FruR and PdhR, which showed a consistent response considering media composition.
  
  
  CONCLUSIONS
  This work allowed the identification of eight interconnected regulatory network modules that includes CRP, Fis and other transcriptional factors that respond directly or indirectly to the presence of glucose. In most cases, each of these modules includes genes encoding physiologically related functions, thus indicating a connection between regulatory network topology and related cellular functions involved in nutrient sensing and metabolism.
authors.affiliation: Departamentos de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apdo. Postal 510-3, Cuernavaca, Morelos, México. rmaria@ibt.unam.mx
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Gutierrez-Ríos
authors.forename: Julio A
authors.initials: JA
authors.lastname: Freyre-Gonzalez
authors.forename: Osbaldo
authors.initials: O
authors.lastname: Resendis
authors.forename: Julio
authors.initials: J
authors.lastname: Collado-Vides
authors.forename: Milton
authors.initials: M
authors.lastname: Saier
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gosset
mesh_terms: D016000:Cluster Analysis; D003470:Culture Media / Q000737:chemistry; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology; D035021:Factor For Inversion Stimulation Protein / Q000502:physiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology*; D053263:Gene Regulatory Networks; D005947:Glucose / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018085:Regulon; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D003470:Culture Media; D002373:Cyclic AMP Receptor Protein; D029968:Escherichia coli Proteins; D035021:Factor For Inversion Stimulation Protein; C501034:Fis protein, E coli; D012329:RNA, Bacterial; D012333:RNA, Messenger; D014157:Transcription Factors; C481662:crp protein, E coli; D005947:Glucose