The Mating-Type Proteins of Fission Yeast Induce Meiosis by Directly Activating mei3 Transcription

ABSTRACT

Cell type control of meiotic gene regulation in the budding yeastSaccharomyces cerevisiae is mediated by a cascade of transcriptional repressors, a1-α2 and Rme1. Here, we investigate the analogous regulatory pathway in the fission yeastSchizosaccharomyces pombe by analyzing the promoter ofmei3, the single gene whose expression is sufficient to trigger meiosis. The mei3 promoter does not appear to contain a negative regulatory element that represses transcription in haploid cells. Instead, correct regulation of mei3transcription depends on a complex promoter that contains at least five positive elements upstream of the TATA sequence. These elements synergistically activate mei3 transcription, thereby constituting an on-off switch for the meiosis pathway. Element C is a large region containing multiple sequences that resemble binding sites for M_c, an HMG domain protein encoded by the mating-type locus. The function of element C is extremely sensitive to spacing changes but not to linker-scanning mutations, suggesting the possibility that M_c functions as an architectural transcription factor. Altered-specificity experiments indicate that element D interacts with P_m, a homeodomain protein encoded by the mating-type locus. This indicates that P_m functions as a direct activator of the meiosis pathway, whereas the homologous mating-type protein in S. cerevisiae (α2) functions as a repressor. Thus, despite the strong similarities between the mating-type loci of S. cerevisiae and S. pombe, the regulatory logic that governs the tight control of the key meiosis-inducing genes in these organisms is completely different.

ACKNOWLEDGMENTS

We are indebted to Vicki Chandler and Jo Ann Wise for permitting W.J.v.H. to carry out some of these experiments in their laboratories. We thank Charles Hoffman, Amar Klar, Maureen McLeod, Fred Ponticelli, Fred Winston, and Jo Ann Wise for plasmids and/or yeast strains. We thank Fred Ponticelli for technical advice in the early stages of this work and Brendan Cormack, Mark Lee, and Jo Ann Wise for comments on the manuscript. This work was supported by a predoctoral fellowship to W.J.V.H. from the Howard Hughes Medical Institute, a National Institutes of Health (NIH) postdoctoral fellowship to D.R.D., and research grants to K.S. from NIH (GM30186 and GM53720).