title: Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters.
abstract: BACKGROUND
  The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes.
  
  
  RESULTS
  We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters.
  
  
  CONCLUSIONS
  The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.
authors: Research Unit on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain. malba@imim.es
authors: Nicolás
authors: N
authors: Bellora
authors: Domènec
authors: D
authors: Farré
authors: M Mar
authors: MM
authors: Albà
mesh_terms: D000818:Animals; D030561:Databases, Nucleic Acid; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D009928:Organ Specificity / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012984:Software; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors