title: Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network.
abstract: BACKGROUND
  Transcriptional regulation of cellular functions is carried out through a complex network of interactions among transcription factors and the promoter regions of genes and operons regulated by them. To better understand the system-level function of such networks simplification of their architecture was previously achieved by identifying the motifs present in the network, which are small, overrepresented, topologically distinct regulatory interaction patterns (subgraphs). However, the interaction of such motifs with each other, and their form of integration into the full network has not been previously examined.
  
  
  RESULTS
  By studying the transcriptional regulatory network of the bacterium, Escherichia coli, we demonstrate that the two previously identified motif types in the network (i.e., feed-forward loops and bi-fan motifs) do not exist in isolation, but rather aggregate into homologous motif clusters that largely overlap with known biological functions. Moreover, these clusters further coalesce into a supercluster, thus establishing distinct topological hierarchies that show global statistical properties similar to the whole network. Targeted removal of motif links disintegrates the network into small, isolated clusters, while random disruptions of equal number of links do not cause such an effect.
  
  
  CONCLUSIONS
  Individual motifs aggregate into homologous motif clusters and a supercluster forming the backbone of the E. coli transcriptional regulatory network and play a central role in defining its global topological organization.
authors.affiliation: Department of Pathology, Northwestern University, Chicago, IL 60611, USA. r-dobrin@northwestern.edu
authors.forename: Radu
authors.initials: R
authors.lastname: Dobrin
authors.forename: Qasim K
authors.initials: QK
authors.lastname: Beg
authors.forename: Albert-László
authors.initials: AL
authors.lastname: Barabási
authors.forename: Zoltán N
authors.initials: ZN
authors.lastname: Oltvai
mesh_terms: D001482:Base Composition / Q000235:genetics*; D016000:Cluster Analysis; D019295:Computational Biology / Q000706:statistics & numerical data; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial