Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Microbiol Mol Biol Rev. 2012 Mar;76(1):1-15. doi: 10.1128/MMBR.05010-11.
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.
细胞在个体发育过程中会遇到许多诱导细胞分裂、分化和凋亡的信号。这些信号需要在特定的时间间隔内存在，以诱导细胞表型的稳定变化。诱导信号不再需要完成分化程序的时间点可以称为“决定点”。酵母 Saccharomyces cerevisiae 中的减数分裂发育（孢子形成）提供了研究决定的模型系统。与多细胞生物中的分化程序相似，酵母中的孢子形成程序受到转录级联的调控，该级联产生早期、中期和晚期的孢子特异性转录本。尽管在早期基因表达时就会发生关键的减数特异性事件，但直到中间基因被诱导后才会发生决定。中间启动子被 Ndt80 转录因子激活，该因子在大多数中间基因表达之前产生并激活。在本文中，我讨论了 Ndt80 与减数分裂决定之间的联系。转录调控途径使 Ndt80 转录依赖于早期基因的表达。一旦产生了 Ndt80，重组（粗线期）检查点就会阻止 Ndt80 蛋白的激活。一旦被激活，Ndt80 就会触发一个正反馈回路，导致促进进入前期、减数分裂和孢子形成的基因的诱导。该途径受多个正反馈回路控制，这些回路赋予决定过渡的开关特性。讨论了减数分裂决定途径的调控成分的保守性以及最近报道的 Ndt80 增加复制寿命的能力。
