We present here a new computational method for discovering cis-regulatory e
lements that circumvents the need to cluster genes based on their expressio
n profiles. Based on a model in which upstream motifs contribute additively
to the log-expression level of a gene, this method requires a single genom
e-wide set of expression ratios and the upstream sequence for each gene, an
d outputs statistically significant motifs. Analysis of publicly available
expression data for Saccharomyces cerevisiae reveals several new putative r
egulatory elements, some of which plausibly control the early, transient in
duction of genes during sporulation. Known motifs generally have high stati
stical significance.