The Sum1/Ndt80 Transcriptional Switch and Commitment to Meiosis in Saccharomyces cerevisiae

Abstract

SUMMARY Cells encounter numerous signals during the development of an organism that induce division, differentiation, and apoptosis. These signals need to be present for defined intervals in order to induce stable changes in the cellular phenotype. The point after which an inducing signal is no longer needed for completion of a differentiation program can be termed the “commitment point.” Meiotic development in the yeast Saccharomyces cerevisiae (sporulation) provides a model system to study commitment. Similar to differentiation programs in multicellular organisms, the sporulation program in yeast is regulated by a transcriptional cascade that produces early, middle, and late sets of sporulation-specific transcripts. Although critical meiosis-specific events occur as early genes are expressed, commitment does not take place until middle genes are induced. Middle promoters are activated by the Ndt80 transcription factor, which is produced and activated shortly before most middle genes are expressed. In this article, I discuss the connection between Ndt80 and meiotic commitment. A transcriptional regulatory pathway makes NDT80 transcription contingent on the prior expression of early genes. Once Ndt80 is produced, the recombination (pachytene) checkpoint prevents activation of the Ndt80 protein. Upon activation, Ndt80 triggers a positive autoregulatory loop that leads to the induction of genes that promote exit from prophase, the meiotic divisions, and spore formation. The pathway is controlled by multiple feed-forward loops that give switch-like properties to the commitment transition. The conservation of regulatory components of the meiotic commitment pathway and the recently reported ability of Ndt80 to increase replicative life span are discussed.

Developmental Coordination of Gamete Differentiation with Programmed Cell Death in Sporulating Yeast

“…Numerous studies have suggested that NDT80 controls the commitment to meiosis and spore formation (28). Our findings identify a transition in mother cell vacuolar dynamics as an additional downstream consequence of NDT80-mediated commitment to gametogenesis.…”

Activation of the Smk1 Mitogen-Activated Protein Kinase by Developmentally Regulated Autophosphorylation

“…Taken together, these findings suggest that the accumulation of partially activated Smk1-T207p is largely controlled by NDT80. Despite the tight connection between the transcriptional cascade of sporulation and the accumulation of the monophosphorylated form of Smk1, it should be pointed out that all of the experiments in this study were carried out in the absence of environmental glucose and nitrogen, which are known to negatively regulate other protein kinases that control meiotic processes (39). Whether the phosphorylation of Smk1 on T207 is controlled by nutritionally regulated signaling pathways independent of the transcriptional cascade remains to be established.…”

“…This set of genes is expressed as cells exit meiotic prophase, enter the meiotic divisions (MI/MII), and form spores (38). Middle gene induction is controlled by the opposing activities of a transcriptional repressor named Sum1 and a meiosis-specific transcriptional activator named Ndt80 (39). Sum1 and Ndt80 bind elements in middle promoters termed middle sporulation elements (MSEs) in a mutually exclusive (competitive) fashion (40).…”

Ndt80 activates the meiotic ORC1 transcript isoform and SMA2 via a bi-directional middle sporulation element in Saccharomyces cerevisiae

“…16,17 NDT80 is transcriptionally activated during meiotic prophase I in a 2-step process, whereby the gene is first de-repressed prior to meiotic M-phase I, when Ume6 and Sum1 activities are progressively down-regulated, and then strongly induced via an auto-activating loop when cells trigger the meiotic divisions; 18 reviewed in. 19 Ndt80 target promoters were identified in a large-scale in vivo protein-DNA binding assay of samples from sporulating cells. 20 This experiment, together with position weight matrices (PWMs), which represent patterns such as transcription factor target motifs in DNA sequences, identified genes that are likely regulated by Ndt80.…”