title: Crosstalk between transcription factors and microRNAs in human protein interaction network.
abstract: BACKGROUND
  Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene regulators. Recent studies have suggested that these two kinds of regulators share similar regulatory logics and participate in cooperative activities in the gene regulatory network; however, their combinational regulatory effects and preferences on the protein interaction network remain unclear.
  
  
  METHODS
  In this study, we constructed a global human gene regulatory network comprising both transcriptional and post-transcriptional regulatory relationships, and integrated the protein interactome into this network. We then screened the integrated network for four types of regulatory motifs: single-regulation, co-regulation, crosstalk, and independent, and investigated their topological properties in the protein interaction network.
  
  
  RESULTS
  Among the four types of network motifs, the crosstalk was found to have the most enriched protein-protein interactions in their downstream regulatory targets. The topological properties of these motifs also revealed that they target crucial proteins in the protein interaction network and may serve important roles of biological functions.
  
  
  CONCLUSIONS
  Altogether, these results reveal the combinatorial regulatory patterns of transcription factors and microRNAs on the protein interactome, and provide further evidence to suggest the connection between gene regulatory network and protein interaction network.
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Chen-Ching
authors.initials: CC
authors.lastname: Lin
authors.forename: Ya-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Cho-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Oyang
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
authors.forename: Hsuan-Cheng
authors.initials: HC
authors.lastname: Huang
mesh_terms: D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology*; D049490:Systems Biology / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors