The Ime2 Protein Kinase Enhances the Disassociation of the Sum1 Repressor from Middle Meiotic Promoters

Abstract

Meiotic development in Saccharomyces cerevisiae (sporulation) is controlled by the sequential transcription of temporally distinct sets of meiosis-specific genes. The induction of middle genes controls exit from meiotic prophase, the completion of the nuclear divisions, and spore formation. Middle promoters are controlled through DNA elements termed middle sporulation elements (MSEs) that are bound by the Sum1 repressor during vegetative growth and by the Ndt80 activator during meiosis. It has been proposed that the induction of middle promoters is controlled by competition between Ndt80 and Sum1 for MSE occupancy. Here, we show that the Sum1 repressor can be removed from middle promoters in meiotic cells independent of Ndt80 expression. This process requires the phosphorylation of Sum1 by the meiosis-specific cyclin-dependent kinase-like kinase Ime2. The deletion of HST1, which encodes a Sir2 paralog that interacts with Sum1, bypasses the requirement for this phosphorylation. These findings suggest that in the presence of Ndt80, Sum1 may be displaced from MSEs through a competition-based mechanism but that in the absence of Ndt80, Sum1 is removed from chromatin in a separate pathway requiring the phosphorylation of Sum1 by Ime2 and the inhibition of Hst1.Meiotic development is the pathway that produces haploid gametes from diploid precursors. Following the induction of the pathway, cells duplicate the genome and then enter an elongated prophase when homolog pairing, synapsis, and genetic recombination take place. Exit from prophase is followed by two sequential rounds of chromosome segregation. In many organisms, exit from prophase is a key control point where meiotic progression is regulated.Meiotic development in the yeast Saccharomyces cerevisiae (sporulation) is tightly regulated by a transcriptional program. The transcriptional program of sporulation is characterized by the sequential expression of temporally distinct sets of genes that are induced as different steps in the program take place (5, 30). Although there are at least 12 temporally distinct subclasses of sporulation-specific genes, they can be broadly grouped into early, middle, and late classes (reviewed in reference 39).Early promoters are activated by the Ime1 transcription factor, which is expressed and activated in diploids in response to starvation signals (reviewed in references 13 and 39). Early genes are expressed throughout meiotic S phase and prophase (5, 30). Toward the end of prophase, at the pachytene stage, homologs are fully connected by synaptonemal complexes (SCs), joint molecules have been formed but crossover recombinants have not been resolved (1, 24), and the spindle pole body (centrosome) has duplicated in preparation for the first meiotic division (3, 43).Exit from pachytene, entry into the meiotic divisions, and spore formation require the induction of middle genes. Middle promoters are activated by the Ndt80 transcription factor, which specifically binds to DNA elements termed middle sporulation elements (MSEs) (6,8). n...

Meiotic Regulators Ndt80 and Ime2 Have Different Roles in Saccharomyces and Neurospora

“…Surprisingly, a deletion strain of the protein kinase ime-2, a major positive regulator of meiosis in S. cerevisiae, was fertile. In S. cerevisiae, Ime2 activates NDT80 expression by phosphorylation of the repressor Sum1, thereby removing Sum1 from NDT80 promoters and allowing NDT80 expression (Pak and Segall 2002a;Ahmed et al 2009). In N. crassa, Dime-2 mutants were unaffected in expression of fsd-1 during development of asci and ascospores.…”

Sporulation in the Budding Yeast Saccharomyces cerevisiae

“…Full expression requires positive feedback in which the newly synthesized Ndt80 protein displaces Sum1 from the NDT80 promoter and leads to even higher levels of NDT80 expression (Pak and Segall 2002a;Pierce et al 2003). Similarly at other Ndt80-regulated genes, a combination of competition from Ndt80 and phosphorylation by Ime2 is thought to displace Sum1 from the MSE elements and activate transcription Ahmed et al 2009). Whether or not this displacement occurs at all Ndt80-regulated genes is not yet clear.…”

“…Relief of SUM1 repression provides the basis for some controls on NDT80 expression. For instance, the cell cycle kinases Cdc28 and Ime2 redundantly regulate NDT80 induction by phosphorylating Sum1 (Ahmed et al 2009;Shin et al 2010). Mutating phosphorylation sites for either kinase has no phenotype, but mutation of both sets of phosphorylation sites on Sum1 blocks the expression of middle genes (Shin et al 2010).…”

Investigating Host Induced Meiosis in a Fungal Plant Pathogen

“…After the initiation of meiosis, the UME6 repressor complex is replaced with UME6-IME1, but expression is still repressed by the MSE (Pak and Segall, 2002a). IME2 and CDK1 phosphorylate SUM1, leading to its release from the MSE and relieving its repression of Ndt80 (Ahmed et al, 2009;Pak & Segall, 2002a;Shin et al, 2010). This allows for low level Ndt80 expression, stimulated by IME1 at URS1.…”