Unexpected complexity of the budding yeast transcriptome.

The genome of the budding yeast Saccharomyces cerevisiae was sequenced over a decade ago and has been annotated to encode approximately 6,000 genes. However, recent high throughput studies using tiling array hybridization and cDNA sequencing have revealed an unexpectedly large number of previously undescribed transcripts. They largely lack protein-coding capacity and are transcribed from both strands of intragenic and intergenic regions in the genome. Accordingly, pervasive transcription leading to a plethora of noncoding RNAs, which was first revealed for mammalian genomes to attract intense attentions, is likely an intrinsic feature of eukaryotic genomes. Although it is not clear what fraction of these transcription events are functional, some were shown to induce transcriptional interference or histone modifications to regulate gene expression. The budding yeast may serve as an excellent model to study pervasive transcription and noncoding RNAs.

Analysis of gene network regulating yeast multidrug resistance by artificial activation of transcription factors: involvement of Pdr3 in salt tolerance.

We established a strategy to constitutively activate Zn(2)Cys(6)-type protein by fusing its DNA-binding domain with the VP16 trans-activation domain. To explore gene network regulating yeast multidrug resistance, the strategy was applied to Pdr1, Pdr3 and Yrr1, known to regulate multidrug resistance, as well as three uncharacterized Yrr1-related transcription factors. DNA microarray analysis revealed that all of the six mutants induce typical drug transporter genes including SNQ2 and YOR1, suggesting redundancy in regulation. On the other hand, each displays a unique spectrum of targets, which is coincident with the phylogenetic tree of the transcription factors and presumably reflects their functional specification. Indeed, careful analysis of target genes specific to each transcription factor led us to reveal an unexpected role for Pdr3 in salt tolerance. The strategy would thus contribute not only to identify target genes but to reveal redundancy and specificity in complex gene regulatory networks.