title: Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle 98195-7350, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.forename: P T
authors.initials: PT
authors.lastname: Spellman
authors.forename: T
authors.initials: T
authors.lastname: Volpe
authors.forename: P O
authors.initials: PO
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Botstein
authors.forename: T N
authors.initials: TN
authors.lastname: Davis
authors.forename: B
authors.initials: B
authors.lastname: Futcher
mesh_terms: D001665:Binding Sites; D019926:Cyclin B / Q000235:genetics; D004271:DNA, Fungal / Q000378:metabolism; D051858:Forkhead Transcription Factors; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D018816:Genes, cdc; D005810:Multigene Family; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D004271:DNA, Fungal; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors