title: Correlating overrepresented upstream motifs to gene expression: a computational approach to regulatory element discovery in eukaryotes.
abstract: BACKGROUND
  Gene regulation in eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory elements in the upstream region of eukaryotic genes. The genes are grouped in sets sharing an overrepresented short motif in their upstream sequence. For each set, the average expression level from a microarray experiment is determined: If this level is significantly higher or lower than the average taken over the whole genome, then the overerpresented motif shared by the genes in the set is likely to play a role in their regulation.
  
  
  RESULTS
  The method was tested by applying it to the genome of Saccharomyces cerevisiae, using the publicly available results of a DNA microarray experiment, in which expression levels for virtually all the genes were measured during the diauxic shift from fermentation to respiration. Several known motifs were correctly identified, and a new candidate regulatory sequence was determined.
  
  
  CONCLUSIONS
  We have described and successfully tested a simple computational method to identify upstream motifs relevant to gene regulation in eukaryotes by studying the statistical correlation between overepresented upstream motifs and gene expression levels.
authors.affiliation: Dipartimento di Fisica Teorica, Università di Torino, and INFN, Sezione di Torino, Torino, Italy. caselle@to.infn.it
authors.forename: Michele
authors.initials: M
authors.lastname: Caselle
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D001482:Base Composition / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics; D005057:Eukaryotic Cells / Q000737:chemistry / Q000378:metabolism; D005189:False Positive Reactions; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics*; D016681:Genome, Fungal; D016366:Open Reading Frames / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C085976:MIG1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C089979:UME6 protein, S cerevisiae