Abstract
There are about 800 genes in Saccharomyces cerevisiae whose transcription is cell-cycle regulated1,2. Some of these form clusters of co-regulated genes1. The ‘CLB2’ cluster contains 33 genes whose transcription peaks early in mitosis, including CLB1, CLB2, SWI5, ACE2, CDC5, CDC20 and other genes important for mitosis1. 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’ cluster1, 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Spellman, P. T. et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273– 3297 (1998).
Cho, R. J. et al. A genome-wide transcriptional analysis of the mitotic cell cycle. Mol. Cell 2, 65–73 (1998).
Althoefer, H., Schleiffer, A., Wassmann, K., Nordheim, A. & Ammerer, G. Mcm1 is required to coordinate G2-specific transcription in Saccharomyces cerevisiae. Mol. Cell. Biol. 15, 5917–5928 ( 1995).
Lydall, D., Ammerer, G. & Nasmyth, K. A new role for MCM1 in yeast: cell cycle regulation of SWI5 transcription. Genes Dev. 5, 2405 –2419 (1991).
Maher, M., Cong, F., Kindelberger, D., Nasmyth, K. & Dalton, S. Cell cycle-regulated transcription of the CLB2 gene is dependent on Mcm1 and a ternary complex factor. Mol. Cell. Biol. 15, 3129–3137 (1995).
Seufert, W., Futcher, B. & Jentsch, S. Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins. Nature 373, 78 –81 (1995).
Moll, T., Tebb, G., Surana, U., Robitsch, H. & Nasmyth, K. The role of phosphorylation and the CDC28 protein kinase in cell cycle- regulated nuclear import of the S. cerevisiae transcription factor SWI5. Cell 66, 743– 758 (1991).
Dohrmann, P. R. et al. Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Genes Dev. 6, 93–104 ( 1992).
Kovacech, B., Nasmyth, K. & Schuster, T. EGT2 gene transcription is induced predominantly by Swi5 in early G1. Mol. Cell. Biol. 16, 3264 –3274 (1996).
Knapp, D., Bhoite, L., Stillman, D. J. & Nasmyth, K. The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1. Mol. Cell. Biol. 16, 5701– 5707 (1996).
Hecht, A. & Grunstein, M. Mapping DNA interaction sites of chromosomal proteins using immunoprecipitation and polymerase chain reaction. Methods Enzymol. 304, 399– 314 (1999).
Zhu, G. & Davis, T. N. The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the yeast spindle pole body. Biochim. Biophys. Acta 1448, 236–244 ( 1998).
Gimeno, C. J., Ljungdahl, P. O., Styles, C. A. & Fink, G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell 68, 1077–1090 (1992).
Liu, H., Styles, C. A. & Fink, G. R. Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Science 262, 1741–1744 (1993).
Kron, S. J., Styles, C. A. & Fink, G. R. Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae. Mol. Biol. Cell 5, 1003–1022 (1994).
Edgington, N. P., Blacketer, M. J., Bierwagen, T. A. & Myers, A. M. Control of Saccharomyces cerevisiae filamentous growth by cyclin-dependent kinase Cdc28. Mol. Cell. Biol. 19, 1369– 1380 (1999).
Amon, A., Tyers, M., Futcher, B. & Nasmyth, K. Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins. Cell 74, 993–1007 (1993).
Grallert, A., Grallert, B., Ribar, B. & Sipiczki, M. Coordination of initiation of nuclear division and initiation of cell division in Schizosaccharomyces pombe: genetic interactions of mutations. J. Bacteriol. 180, 892–900 (1998).
King, L. & Butler, G. Ace2p, a regulator of CTS1 (chitinase) expression, affects pseudohyphal production in Saccharomyces cerevisiae . Curr. Genet. 34, 183– 191 (1998).
Weigel, D., Jurgens, G., Kuttner, F., Seifert, E. & Jackle, H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell 57, 645–658 (1989).
Kaufmann, E. & Knochel, W. Five years on the wings of fork head. Mech. Dev. 57, 3– 20 (1996).
Lai, E., Clark, K. L., Burley, S. K. & Darnell, J. E. Hepatocyte nuclear factor 3/fork head or "winged helix" proteins: a family of transcription factors of diverse biologic function. Proc. Natl Acad. Sci. USA 90, 10421– 10423 (1993).
Cogswell, J. P., Godlevski, M. M., Bonham, M., Bisi, J. & Babiss, L. Upstream stimulatory factor regulates expression of the cell cycle-dependent cyclin B1 gene promoter. Mol. Cell. Biol. 15, 2782–2790 (1995).
Hwang, A., Maity, A., McKenna, W. G. & Muschel, R. J. Cell cycle-dependent regulation of the cyclin B1 promoter. J. Biol. Chem. 270, 28419–28424 ( 1995).
Overdier, D. G., Porcella, A. & Costa, R. H. The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol. Cell. Biol. 14, 2755–2766 (1994).
Gimeno, C. J. & Fink, G. R. Induction of pseudohyphal growth by overexpression of PHD1, a Saccharomyces cerevisiae gene related to transcriptional regulators of fungal development. Mol. Cell. Biol. 14, 2100–2112 ( 1994).
Acknowledgements
We thank G. Fink for strains and H. Wijnen for reading the manuscript. This work was supported by grants from the NIH to T.D., D.B., P.B. and B.F.
Author information
Authors and Affiliations
Corresponding author
Supplementary Information
Supplementary information
Supplementary Information
Supplementary Information (PDF 153 kb)
Rights and permissions
About this article
Cite this article
Zhu, G., Spellman, P., Volpe, T. et al. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth . Nature 406, 90–94 (2000). https://doi.org/10.1038/35017581
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/35017581
This article is cited by
-
Cyclin/Forkhead-mediated coordination of cyclin waves: an autonomous oscillator rationalizing the quantitative model of Cdk control for budding yeast
npj Systems Biology and Applications (2021)
-
Quantitative model of eukaryotic Cdk control through the Forkhead CONTROLLER
npj Systems Biology and Applications (2021)
-
Forkhead transcription factor Fkh1: insights into functional regulatory domains crucial for recruitment of Sin3 histone deacetylase complex
Current Genetics (2021)
-
Improved recovery of cell-cycle gene expression in Saccharomyces cerevisiae from regulatory interactions in multiple omics data
BMC Genomics (2020)
-
Transcriptional control of fungal cell cycle and cellular events by Fkh2, a forkhead transcription factor in an insect pathogen
Scientific Reports (2015)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.