Zhu G, Spellman P T, Volpe T, Brown P O, Botstein D, Davis T N, Futcher B
Department of Biochemistry, University of Washington, Seattle 98195-7350, USA.
Nature. 2000 Jul 6;406(6791):90-4. doi: 10.1038/35017581.
There are about 800 genes in Saccharomyces cerevisiae whose transcription is cell-cycle regulated. Some of these form clusters of co-regulated genes. The 'CLB2' cluster contains 33 genes whose transcription peaks early in mitosis, including CLB1, CLB2, SWI5, ACE2, CDC5, CDC20 and other genes important for mitosis. Here we find that the genes in this cluster lose their cell cycle regulation in a mutant that lacks two forkhead transcription factors, Fkh1 and Fkh2. Fkh2 protein is associated with the promoters of CLB2, SWI5 and other genes of the cluster. These results indicate that Fkh proteins are transcription factors for the CLB2 cluster. The fkh1 fkh2 mutant also displays aberrant regulation of the 'SIC1' cluster, whose member genes are expressed in the M-G1 interval and are involved in mitotic exit. This aberrant regulation may be due to aberrant expression of the transcription factors Swi5 and Ace2, which are members of the CLB2 cluster and controllers of the SIC1 cluster. Thus, a cascade of transcription factors operates late in the cell cycle. Finally, the fkh1 fkh2 mutant displays a constitutive pseudohyphal morphology, indicating that Fkh1 and Fkh2 may help control the switch to this mode of growth.
酿酒酵母中约有800个基因的转录受细胞周期调控。其中一些形成了共调控基因簇。“CLB2”簇包含33个基因，其转录在有丝分裂早期达到峰值，包括CLB1、CLB2、SWI5、ACE2、CDC5、CDC20以及其他对有丝分裂重要的基因。我们发现，在一个缺乏两个叉头转录因子Fkh1和Fkh2的突变体中，该簇中的基因失去了细胞周期调控。Fkh2蛋白与CLB2、SWI5以及该簇中其他基因的启动子相关联。这些结果表明，Fkh蛋白是CLB2簇的转录因子。fkh1 fkh2突变体还表现出“SIC1”簇的异常调控，该簇的成员基因在M-G1间期表达并参与有丝分裂退出。这种异常调控可能是由于转录因子Swi5和Ace2的异常表达，它们是CLB2簇的成员且是SIC1簇的调控因子。因此，一系列转录因子在细胞周期后期发挥作用。最后，fkh1 fkh2突变体表现出组成型假菌丝形态，表明Fkh1和Fkh2可能有助于控制向这种生长模式的转变。
