title: DWE: discriminating word enumerator.
abstract: BACKGROUND
  Tissue-specific transcription factor binding sites give insight into tissue-specific transcription regulation.
  
  
  RESULTS
  We describe a word-counting-based tool for de novo tissue-specific transcription factor binding site discovery using expression information in addition to sequence information. We incorporate tissue-specific gene expression through gene classification to positive expression and repressed expression. We present a direct statistical approach to find overrepresented transcription factor binding sites in a foreground promoter sequence set against a background promoter sequence set. Our approach naturally extends to synergistic transcription factor binding site search. We find putative transcription factor binding sites that are overrepresented in the proximal promoters of liver-specific genes relative to proximal promoters of liver-independent genes. Our results indicate that binding sites for hepatocyte nuclear factors (especially HNF-1 and HNF-4) and CCAAT/enhancer-binding protein (C/EBPbeta) are the most overrepresented in proximal promoters of liver-specific genes. Our results suggest that HNF-4 has strong synergistic relationships with HNF-1, HNF-4 and HNF-3beta and with C/EBPbeta.
  
  
  BACKGROUND
  Programs are available for use over the Web at http://rulai.cshl.edu/tools/dwe.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. ps@cs.pdx.edu
authors.forename: Pavel
authors.initials: P
authors.lastname: Sumazin
authors.forename: Gengxin
authors.initials: G
authors.lastname: Chen
authors.forename: Naoya
authors.initials: N
authors.lastname: Hata
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.forename: Theresa
authors.initials: T
authors.lastname: Zhang
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D016384:Consensus Sequence; D017124:Conserved Sequence; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008099:Liver / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors