Computational identification of transcription factor binding sites by functional analysis of sets of genes sharing overrepresented upstream motifs.
BACKGROUND
Transcriptional regulation is a key mechanism in the functioning of the cell, and is mostly effected through transcription factors binding to specific recognition motifs located upstream of the coding region of the regulated gene. The computational identification of such motifs is made easier by the fact that they often appear several times in the upstream region of the regulated genes, so that the number of occurrences of relevant motifs is often significantly larger than expected by pure chance.


RESULTS
To exploit this fact, we construct sets of genes characterized by the statistical overrepresentation of a certain motif in their upstream regions. Then we study the functional characterization of these sets by analyzing their annotation to Gene Ontology terms. For the sets showing a statistically significant specific functional characterization, we conjecture that the upstream motif characterizing the set is a binding site for a transcription factor involved in the regulation of the genes in the set.


CONCLUSIONS
The method we propose is able to identify many known binding sites in S. cerevisiae and new candidate targets of regulation by known transcription factors. Its application to less well studied organisms is likely to be valuable in the exploration of their regulatory interaction network.
Corà
Davide
D
Dipartimento di Fisica Teorica, Università di Torino, and INFN, sezione di Torino, Italy. cora@to.infn.it
Di Cunto
Ferdinando
F
Provero
Paolo
P
Silengo
Lorenzo
L
Caselle
Michele
M
D024506:5' Flanking Region / Q000235:genetics*; D001482:Base Composition / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D019295:Computational Biology / Q000379:methods*; D016384:Consensus Sequence / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics* / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D024363:Transcription Initiation Site
D004271:DNA, Fungal; D014157:Transcription Factors