title: Coregulation of transcription factors and microRNAs in human transcriptional regulatory network.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the post-transcriptional level. Recent studies have suggested that miRNAs and transcription factors are primary metazoan gene regulators; however, the crosstalk between them still remains unclear.
  
  
  METHODS
  We proposed a novel model utilizing functional annotation information to identify significant coregulation between transcriptional and post-transcriptional layers. Based on this model, function-enriched coregulation relationships were discovered and combined into different kinds of functional coregulation networks.
  
  
  RESULTS
  We found that miRNAs may engage in a wider diversity of biological processes by coordinating with transcription factors, and this kind of cross-layer coregulation may have higher specificity than intra-layer coregulation. In addition, the coregulation networks reveal several types of network motifs, including feed-forward loops and massive upstream crosstalk. Finally, the expression patterns of these coregulation pairs in normal and tumour tissues were analyzed. Different coregulation types show unique expression correlation trends. More importantly, the disruption of coregulation may be associated with cancers.
  
  
  CONCLUSIONS
  Our findings elucidate the combinatorial and cooperative properties of transcription factors and miRNAs regulation, and we proposes that the coordinated regulation may play an important role in many biological processes.
authors.affiliation: Institute of Biomedical Informatics, Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan. joeychen@gate.sinica.edu.tw
authors.forename: Cho-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Shui-Tein
authors.initials: ST
authors.lastname: Chen
authors.forename: Chiou-Shann
authors.initials: CS
authors.lastname: Fuh
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
authors.forename: Hsuan-Cheng
authors.initials: HC
authors.lastname: Huang
mesh_terms: D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D012323:RNA Processing, Post-Transcriptional; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors