title: Analog regulation of metabolic demand.
abstract: BACKGROUND
  The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs) from a metabolic and transcriptional regulatory network perspective.
  
  
  RESULTS
  We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants), this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN), as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants.
  
  
  CONCLUSIONS
  So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our results show that DNA supercoiling coordinates gene expression with metabolism. Furthermore, this control is acting directly because we can exclude the potential role of the TRN as a mediator.
authors.affiliation: Jacobs University Bremen, 28759 Bremen, Germany. n.sonnenschein@jacobs-university.de
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Sonnenschein
authors.forename: Marcel
authors.initials: M
authors.lastname: Geertz
authors.forename: Georgi
authors.initials: G
authors.lastname: Muskhelishvili
authors.forename: Marc-Thorsten
authors.initials: MT
authors.lastname: Hütt
mesh_terms: D002876:Chromosomes, Bacterial / Q000235:genetics*; D004278:DNA, Superhelical / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology*; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology*; D046228:Microarray Analysis
chemical_list: D004278:DNA, Superhelical; D004268:DNA-Binding Proteins