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Molecular and Cellular Biology, February 2007, p. 818-829, Vol. 27, No. 3
0270-7306/07/$08.00+0     doi:10.1128/MCB.00439-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of Transcription Factor Kar4 in Regulating Downstream Events in the Saccharomyces cerevisiae Pheromone Response Pathway{triangledown}

Ron Lahav,{dagger} Alison Gammie, Saeed Tavazoie, and Mark D. Rose*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Received 13 March 2006/ Returned for modification 24 May 2006/ Accepted 6 November 2006

Yeast Kar4 is a putative transcription factor required for karyogamy (the fusion of haploid nuclei during mating) and possibly other functions. Previously known to be required only for the transcriptional induction of KAR3 and CIK1, microarray experiments identified many genes regulated by Kar4 in both mating and mitosis. Several gene clusters are positively or negatively regulated by mating pheromone in a Kar4-dependent manner. Chromatin immunoprecipitation and gel shift assays confirmed that Kar4 binds to regulatory DNA sequences upstream of KAR3. Together with one-hybrid experiments, these data support a model in which both Kar4 and Ste12 bind jointly to the KAR3 promoter. Analysis of the upstream regions of Kar4-induced genes identified a DNA sequence motif that may be a binding site for Kar4. Mutation within the motif upstream of KAR3 eliminated pheromone induction. Genes regulated by Kar4, on average, are delayed in their temporal expression and exhibit a more stringent dose response to pheromone. Furthermore, the induction of Kar4 by pheromone is necessary for the delayed temporal induction of KAR3 and PRM2, genes required for efficient nuclear fusion during mating. Accordingly, we propose that Kar4 plays a critical role in the choreography of the mating response.

* Corresponding author. Mailing address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014. Phone: (609) 258-2804. Fax: (609) 258-6175. E-mail: mrose{at}molbio.princeton.edu.

{triangledown} Published ahead of print on 13 November 2006.

{dagger} Present address: AnorMed, Inc., Langley, British Columbia V2Y 1N5, Canada.

Molecular and Cellular Biology, February 2007, p. 818-829, Vol. 27, No. 3
0270-7306/07/$08.00+0     doi:10.1128/MCB.00439-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ydenberg, C. A., Rose, M. D. (2009). Antagonistic regulation of Fus2p nuclear localization by pheromone signaling and the cell cycle. JCB 184: 409-422 [Abstract] [Full Text]  
  • Schaefer, D., Cote, P., Whiteway, M., Bennett, R. J. (2007). Barrier Activity in Candida albicans Mediates Pheromone Degradation and Promotes Mating. Eukaryot Cell 6: 907-918 [Abstract] [Full Text]  


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