  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. 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.
