title: Rigorous and thorough bioinformatic analyses of olfactory receptor promoters confirm enrichment of O/E and homeodomain binding sites but reveal no new common motifs.
abstract: BACKGROUND
  Mammalian olfactory receptors (ORs) are subject to a remarkable but poorly understood regime of transcriptional regulation, whereby individual olfactory neurons each express only one allele of a single member of the large OR gene family.
  
  
  RESULTS
  We performed a rigorous search for enriched sequence motifs in the largest dataset of OR promoter regions analyzed to date. We combined measures of cross-species conservation with databases of known transcription factor binding sites and ab initio motif-finding algorithms. We found strong enrichment of binding sites for the O/E family of transcription factors and for homeodomain factors, both already known to be involved in the transcriptional control of ORs, but did not identify any novel enriched sequences. We also found that TATA-boxes are present in at least a subset of OR promoters.
  
  
  CONCLUSIONS
  Our rigorous approach provides a template for the analysis of the regulation of large gene families and demonstrates some of the difficulties and pitfalls of such analyses. Although currently available bioinformatics methods cannot detect all transcriptional regulatory elements, our thorough analysis of OR promoters shows that in the case of this gene family, experimental approaches have probably already identified all the binding factors common to large fractions of OR promoters.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. jayoung@fhcrc.org
authors.forename: Janet M
authors.initials: JM
authors.lastname: Young
authors.forename: Ralf M
authors.initials: RM
authors.lastname: Luche
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Trask
mesh_terms: D000465:Algorithms; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics*; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D018035:Receptors, Odorant / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D018035:Receptors, Odorant; D014157:Transcription Factors
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