A competitive transcription factor binding mechanism determines the timing of late cell cycle-dependent gene expression.

Transcriptional control is exerted by the antagonistic activities of activator and repressor proteins. In Saccharomyces cerevisiae, transcription factor complexes containing the MADS box protein Mcm1p are key regulators of cell cycle-dependent transcription at both the G2/M and M/G1 transitions. The homeodomain repressor protein Yox1p acts in a complex with Mcm1p to control the timing of gene expression. Here, we show that Yox1p interacts with Mcm1p through a motif located N terminally to its homeodomain. Yox1p functions as a transcriptional repressor by competing with the forkhead transcription activator protein Fkh2p for binding to Mcm1p through protein-protein interactions at promoters of a subset of Mcm1p-regulated genes. Importantly, this competition is not through binding the same DNA site that is commonly observed. Thus, this study describes a different mechanism for determining the timing of cell cycle-dependent gene expression that involves competition between short peptide motifs in repressor and activator proteins for interaction with a common binding partner.