title: Sequence features of DNA binding sites reveal structural class of associated transcription factor.
abstract: BACKGROUND
  A key goal in molecular biology is to understand the mechanisms by which a cell regulates the transcription of its genes. One important aspect of this transcriptional regulation is the binding of transcription factors (TFs) to their specific cis-regulatory counterparts on the DNA. TFs recognize and bind their DNA counterparts according to the structure of their DNA-binding domains (e.g. zinc finger, leucine zipper, homeodomain). The structure of these domains can be used as a basis for grouping TFs into classes. Although the structure of DNA-binding domains varies widely across TFs generally, the TFs within a particular class bind to DNA in a similar fashion, suggesting the existence of class-specific features in the DNA sequences bound by each class of TFs.
  
  
  RESULTS
  In this paper, we apply a sparse Bayesian learning algorithm to identify a small set of class-specific features in the DNA sequences bound by different classes of TFs; the algorithm simultaneously learns a true multi-class classifier that uses these features to predict the DNA-binding domain of the TF that recognizes a particular set of DNA sequences. We train our algorithm on the six largest classes in TRANSFAC, comprising a total of 587 TFs. We learn a six-class classifier for this training set that achieves 87% leave-one-out cross-validation accuracy. We also identify features within cis-regulatory sequences that are highly specific to each class of TF, which has significant implications for how TF binding sites should be modeled for the purpose of motif discovery.
authors.affiliation: Duke University, Department of Computer Science Box 90129, Durham, NC 27708, USA. lee@cs.duke.edu
authors.forename: Leelavati
authors.initials: L
authors.lastname: Narlikar
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Hartemink
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated / Q000379:methods; D011485:Protein Binding; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000145:classification* / Q000235:genetics
chemical_list: D014157:Transcription Factors; D004247:DNA