Mizuno T, Nakazawa N, Remgsamrarn P, Kunoh T, Oshima Y, Harashima S
Department of Biotechnology, Graduate School of Engineering, Osaka University, Japan.
Curr Genet. 1998 Apr;33(4):239-47. doi: 10.1007/s002940050332.
Ime1 plays a pivotal role in the initiation of meiosis in a/alpha diploid cells of Saccharomyces cerevisiae. In the absence of glucose and nitrogen, IME1 expression is greater in a/alpha cells than in either a or alpha cells and therefore only a/alpha, but not a/a or alpha/alpha, cells are committed to sporulation. It is known that IME1 expression is positively regulated by Mck1, Rim1, Ime4 and the Swi-Snf complex but other factors may also be involved. In addition, Rme1 is assumed to repress IME1 expression. To provide more details of the repression of expression of IME1, we have isolated mutants in which the IME1p-PHO5 fusion gene integrated at the ura3 locus is expressed in alpha cells under nutritionally rich conditions. We found that mutations occurred in TUP1, SSN6, SIN4 and RGR1, among which TUP1 and SSN6 were identified for the first time as negative regulators of IME1 expression. Deletion of the Rme1-binding site from the IME1 promoter did not result in activation of the expression of IME1 under nutritionally rich conditions, suggesting that Rme1 does not function as a DNA-binding protein with the Tup1-Ssn6 repression complex. We also demonstrated that the 294-bp fragment from nucleotide position -914 to -621 and the 301-bp fragment from nucleotide position -1215 to -915 of the IME1 promoter region contain elements acting as URS and UAS in TUP1+ and tup1 mutant cells, respectively. These findings indicate that IME1 is negatively regulated by the Tup1-Ssn6 repressor complex through two distinct upstream regions in conjunction with unidentified DNA-binding proteins.
Ime1在酿酒酵母a/α二倍体细胞减数分裂的起始过程中起着关键作用。在缺乏葡萄糖和氮的情况下,a/α细胞中Ime1的表达量高于a细胞或α细胞,因此只有a/α细胞,而不是a/a或α/α细胞,会进入孢子形成阶段。已知Ime1的表达受到Mck1、Rim1、Ime4和Swi-Snf复合物的正调控,但可能还涉及其他因素。此外,Rme1被认为会抑制Ime1的表达。为了更详细地了解Ime1表达的抑制机制,我们分离了一些突变体,其中整合在ura3位点的Ime1p-PHO5融合基因在营养丰富的条件下能在α细胞中表达。我们发现Tup1、Ssn6、Sin4和Rgr1发生了突变,其中Tup1和Ssn6首次被鉴定为Ime1表达的负调控因子。从Ime1启动子中删除Rme1结合位点,在营养丰富的条件下并不会导致Ime1表达的激活,这表明Rme并不作为一种与Tup1-Ssn6抑制复合物结合的DNA结合蛋白发挥作用。我们还证明,Ime1启动子区域从核苷酸位置-914到-621的294 bp片段和从核苷酸位置-1215到-915的301 bp片段,分别在TUP +和tup1突变体细胞中包含作为URS和UAS起作用的元件。这些发现表明,Ime1受到Tup1-Ssn6抑制复合物通过两个不同的上游区域与未鉴定的DNA结合蛋白共同作用的负调控。