Rpb4, the non-essential core subunit of RNA polymerase II has been assigned a function of regulating stress response in S. cerevisiae based mainly on phenotypes associated with its deletion. The actual mechanism has been elusive, although various hypotheses have been put forth. We have shown previously that it plays a significant role in activation of a subset of genes, rather than causing generalized defect in transcription. We used the microarray technology to look at the effect of this RNA polymerase subunit on the expression pattern of the entire S. cerevisiae genome. Many surprises emerged when we compared the genome-wide expression patterns of wild type and a mutant lacking the RPB4 gene (rpb4Δ) subjected to heat shock. The initial analysis of genes downregulated in the mutant showed that the co-regulation of genes is not position-dependent, although the locus carrying the deletion had unexpectedly a large cluster of down-regulated genes. We also found that among the known down-regulated genes, a majority is involved in hexose uptake and utilization. We speculate that this could potentially contribute to the slow growth rate of the mutant. Compared to the other components of the transcription machinery, the Rpb4 subunit affects a unique set of genes