Abstract
Many cell-cycle-specific events are supported by stage-specific gene expression. In budding yeast, at least three different nuclear factors seem to cooperate in the periodic activation of G2/M-specific genes1,2,3. Here we show, by using chromatin immunoprecipitation polymerase chain reaction assays, that a positive regulator, Ndd1, becomes associated with G2/M promoter regions in manner that depends on the stage in cell cycle. Its recruitment depends on a permanent protein–DNA complex consisting of the MADS box protein, Mcm1, and a recently identified partner Fkh2, a forkhead/winged helix related transcription factor4,5. The lethality of Ndd1 depletion is suppressed by fkh2 null mutations, which indicates that Fkh2 may also have a negative regulatory role in the transcription of G2/M-induced RNAs. We conclude that Ndd1–Fkh2 interactions may be the transcriptionally important process targeted by Cdk activity.
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
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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).
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).
Loy, C. J., Lydall, D. & Surana, U. Ndd1, a high-dosage suppressor of cdc28-1N, is essential for expression of a subset of late-S-phase-specific genes in Saccharomyces cerevisiae. Mol. Cell. Biol. 19, 3312 –3327 (1999).
Zhu, G. et al. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Nature 406, 90– 94 (2000).
Hollenhorst, P. C., Bose, M. E., Mielke, M. R., Müller, U. & Fox, C. A. Forkhead genes in transcriptional silencing, cell morphology and cell cycle: overlapping and distinct funcitons for FKH1 and FKH2 in Saccaromyces cerevisiae. Genetics 154, 1533–1548 (2000).
Nasmyth, K. At the heart of the budding yeast cell cycle. Trends Genet. 12, 405–412 (1996).
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).
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).
Lydall, D., Ammerer, G. & Nasmyth, K. A new role of Mcm1 in yeast: cell cycle regulation of SWI5 transcription. Genes Dev. 5, 2405– 2419 (1991).
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).
Deckert, J., Rodriguez Torres, A. M., Simon, J. T. & Zitomer, R. S. Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae. Mol. Cell. Biol. 15, 6109–6117 (1995).
Di Flumeri, C., Liston, P., Acheson, N. H. & Keng, T. The HMG domain of the ROX1 protein mediates repression of HEM13 through overlapping DNA binding and oligomerization functions. Nucleic Acids Res. 24, 808–815 (1996).
Hecht, A., Strahl-Bolsinger, S. & Grunstein, M. Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature 383, 92–96 (1996).
Cosma, M. P., Tanaka, T. & Nasmyth, K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97, 299–311 ( 1999).
Errede, B. & Ammerer, G. STE12, a protein involved in cell-type-specific transcription and signal transduction in yeast, is part of protein-DNA complexes. Genes Dev. 3, 1349–1361 (1989).
Kaufmann, E. & Knöchel, W. Five years on the wings of fork head. Mech. Dev. 57, 3– 20 (1996).
Biggs, W. H. et al. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc. Natl Acad. Sci. USA 96, 7421–7426 (1999).
Durocher, D., Henkel, J., Fersht, A. & Jackson, S. P. The FHA domainis a modular phosphopeptide recognition motif. Mol. Cell 4, 387–394 (1999).
Knop, M. et al. Epitope tagging of yeast genes using a PCR-based strategy: more tags and improved practical routines. Yeast 15, 963–972 (1999).
Zachariae, W., Shin, T. H., Galova, M., Obermaier, B. & Nasmyth, K. Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae. Science 274, 1201–1204 (1996).
Piatti, S., Bohm, T., Cocker, J. H., Diffley, J. F. & Nasmyth, K. Activation of S-phase-promoting CDKs in late G1 defines a ‘point of no return’ after which Cdc6 synthesis cannot promote DNA replication in yeast. Genes Dev. 10, 1516–1531 (1996).
Acknowledgements
We are especially grateful to B. Futcher for providing us with unpublished information about Fkh1 and Fkh2. We thank U. Surana, K. Nasmyth for plasmids and many helpful discussions; M. Galova for sharing materials; C. Zimmer for strain constructions; T. Tanaka and E. Brabec for help in establishing ChIP assays; A. Gartner and P. Alepuz for comments on the manuscript. This work was supported by the Austrian National Bank and by the Austrian Fonds zur Förderung wissenschaftlicher Forschung.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koranda, M., Schleiffer, A., Endler, L. et al. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature 406, 94–98 (2000). https://doi.org/10.1038/35017589
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/35017589
This article is cited by
-
Conservation of dynamic characteristics of transcriptional regulatory elements in periodic biological processes
BMC Bioinformatics (2022)
-
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)
-
Improved recovery of cell-cycle gene expression in Saccharomyces cerevisiae from regulatory interactions in multiple omics data
BMC Genomics (2020)
-
A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
npj Systems Biology and Applications (2017)
-
Create, activate, destroy, repeat: Cdk1 controls proliferation by limiting transcription factor activity
Current Genetics (2016)
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.