Van Heeckeren W J, Dorris D R, Struhl K
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell Biol. 1998 Dec;18(12):7317-26. doi: 10.1128/MCB.18.12.7317.
Cell type control of meiotic gene regulation in the budding yeast Saccharomyces cerevisiae is mediated by a cascade of transcriptional repressors, a1-alpha2 and Rme1. Here, we investigate the analogous regulatory pathway in the fission yeast Schizosaccharomyces pombe by analyzing the promoter of mei3, 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 mei3 transcription 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 Mc, 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 Mc functions as an architectural transcription factor. Altered-specificity experiments indicate that element D interacts with Pm, a homeodomain protein encoded by the mating-type locus. This indicates that Pm functions as a direct activator of the meiosis pathway, whereas the homologous mating-type protein in S. cerevisiae (alpha2) 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.
芽殖酵母酿酒酵母减数分裂基因调控的细胞类型控制由一系列转录抑制因子a1-alpha2和Rme1介导。在这里,我们通过分析mei3的启动子来研究裂殖酵母粟酒裂殖酵母中的类似调控途径,mei3是其表达足以触发减数分裂的单个基因。mei3启动子似乎不包含在单倍体细胞中抑制转录的负调控元件。相反,mei3转录的正确调控依赖于一个复杂的启动子,该启动子在TATA序列上游至少包含五个正调控元件。这些元件协同激活mei3转录,从而构成减数分裂途径的开关。元件C是一个大区域,包含多个类似于由交配型基因座编码的HMG结构域蛋白Mc的结合位点的序列。元件C的功能对间距变化极其敏感,但对连接子扫描突变不敏感,这表明Mc可能作为一种结构转录因子发挥作用。特异性改变实验表明元件D与由交配型基因座编码的同源结构域蛋白Pm相互作用。这表明Pm作为减数分裂途径的直接激活因子发挥作用,而酿酒酵母中的同源交配型蛋白(alpha2)则作为抑制因子发挥作用。因此,尽管酿酒酵母和粟酒裂殖酵母的交配型基因座之间有很强的相似性,但在这些生物体中控制关键减数分裂诱导基因严格调控的调控逻辑却完全不同。