The Sum1/Ndt80 transcriptional switch and commitment to meiosis in Saccharomyces cerevisiae

Abstract

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.

Fig 1

The transcriptional cascade and commitment. The diagram shows a vegetative precursor cell (left) that has been induced by nutrient deprivation to form a spore (right). The early, middle, and late sets of sporulation-specific genes are shown as horizontal arrows, and the meiotic processes that require these gene sets are shown connected by downward arrows. The commitment point is represented as a vertical dashed line, and the alternative responses (return to vegetative growth [RTG] and completion of the sporulation program [commitment]) are indicated as a function of when the inducing signal (starvation) is eliminated (rich medium is added).

Fig 2

Ndt80 activates multiple processes associated with meiotic commitment and the completion of sporulation. Examples of Ndt80 target genes required for pachytene exit, mono-orientation, MI, MII, and spore formation are shown. The genes shaded in yellow also function in mitotic cells. The genes shaded in blue are repressed by Sum1 in mitotic cells and are meiosis specific.

Fig 3

Sum1 and Ndt80 interact with overlapping sites to control meiotic processes. The core MSE (consensus, 5′-YGNCACAAAA-3′) is shown as a green rectangle that can become bound when the Ndt80 protein is produced in meiotic prophase (A). Sum1 recognizes the core MSE, but additional bases (blue rectangle) generate a composite site (consensus, 5′ AGYGWCACAAAAD) that can be recognized by both Sum1 and Ndt80. Sum1 can be competitively displaced from DNA by Ndt80 during meiotic prophase (B). However, Sum1 can also be removed in the absence of Ndt80 (C). See the text for details. The consensus sites (where N is any base, Y is C or T, and D is A, G, or T) are taken from reference .

Fig 4

The NDT80 transcriptional induction pathway. The sequential steps leading to the expression of the NDT80 promoter are shown. The shaded box represents distinct chromatin structures at the NDT80 promoter that may be generated as the indicated regulatory transitions take place. Although the NDT80 promoter contains 2 URS1s and 2 MSEs (one which is Sum1 repressible and Ndt80 inducible and a second that is exclusively Ndt80 inducible), only a single URS1 and the Sum1-repressible/Ndt80-inducible MSE are shown. Ime1 is present at early (URS1-containing) promoters as they are expressed and is therefore predicted to be present after step 1. However, the mechanism that tethers Ime1 to early promoters is unresolved, and for simplicity its presence at URS1 is not diagrammed. See the text for details.