Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes

In the budding yeast, Saccharomyces cerevisiae, a significant fraction of genes (>10%) are transcribed with cell cycle periodicity. These genes encode critical cell cycle regulators as well as proteins with no direct connection to cell cycle functions. Cell cycle-regulated genes can be organized into 'clusters' exhibiting similar patterns of regulation. In most cases periodic transcription is achieved via both repressive and activating mechanisms. Fine-tuning appears to have evolved by the juxtaposition of regulatory motifs characteristic of more than one cluster within the same promoter. Recent reports have provided significant new insight into the role of the cyclin-dependent kinase Cdk1 (Cdc28) in coordination of transcription with cell cycle events. In early G1, the transcription factor complex known as SBF is maintained in a repressed state by association of the Whi5 protein. Phosphorylation of Whi5 by Cdk1 in late G1 leads to dissociation from SBF and transcriptional derepression. G2/M-specific transcription is achieved by converting the repressor Fkh2 into an activator. Fkh2 serves as a repressor during most of the cell cycle. However, phosphorylation of a cofactor, Ndd1, by Cdk1 late in the cell cycle promotes binding to Fkh2 and conversion into a transcriptional activator. Such insights derived from analysis of specific genes when combined with genome-wide analysis provide a more detailed and integrated view of cell cycle-dependent transcription.