Abstract
Proteins interact with genomic DNA to bring the genome to life; and these interactions also define many functional features of the genome. SBF and MBF are sequence-specific transcription factors that activate gene expression during the G1/S transition of the cell cycle in yeast1,2. SBF is a heterodimer of Swi4 and Swi6, and MBF is a heterodimer of Mbp1 and Swi6 (refs 1, 3). The related Swi4 and Mbp1 proteins are the DNA-binding components of the respective factors, and Swi6 may have a regulatory function4,5. A small number of SBF and MBF target genes have been identified3,6,7,8,9,10. Here we define the genomic binding sites of the SBF and MBF transcription factors in vivo, by using DNA microarrays. In addition to the previously characterized targets, we have identified about 200 new putative targets. Our results support the hypothesis that SBF activated genes are predominantly involved in budding, and in membrane and cell-wall biosynthesis, whereas DNA replication and repair are the dominant functions among MBF activated genes6,11. The functional specialization of these factors may provide a mechanism for independent regulation of distinct molecular processes that normally occur in synchrony during the mitotic cell cycle.
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References
Koch, C., Moll, T., Neuberg, M., Ahorn, H. & Nasmyth, K. A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. Science 261, 1551–1557 (1993).
Koch, C. & Nasmyth, K. Cell cycle regulated transcription in yeast. Curr. Opin. Cell Biol. 6, 451– 459 (1994).
Andrews, B. J. & Herskowitz, I. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription. Nature 342, 830–833 (1989).
Primig, M., Sockanathan, S., Auer, H. & Nasmyth, K. Anatomy of a transcription factor important for the start of the cell cycle in Saccharomyces cerevisiae. Nature 358, 593–597 (1992).
Dirick, L., Moll, T., Auer, H. & Nasmyth, K. A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast. Nature 357, 508–513 (1992).
Lowndes, N. F., Johnson, A. L. & Johnston, L. H. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature 350, 247–250 ( 1991).
Ogas, J., Andrews, B. J. & Herskowitz, I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell 66, 1015 –1026 (1991).
McIntosh, E. M. MCB elements and the regulation of DNA replication genes in yeast. Curr. Genet. 24, 185–192 (1993).
Schwob, E. & Nasmyth, K. CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae . Genes Dev. 7, 1160– 1175 (1993).
Measday, V., Moore, L., Ogas, J., Tyers, M. & Andrews, B. The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle regulator in yeast. Science 266, 1391–1395 (1994).
Igual, J. C., Johnson, A. L. & Johnston, L. H. Coordinated regulation of gene expression by the cell cycle transcription factor Swi4 and the protein kinase C MAP kinase pathway for yeast cell integrity. EMBO J. 15, 5001 –5013 (1996).
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).
Bailey, T. L. & Elkan, C. in Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology 28– 36 (American Association for Artificial Intelligence, Menlo Park, California, 1994).
Stormo, G. D. & Hartzell, G. W. Identifying protein-binding sites from unaligned DNA fragments. Proc. Natl Acad. Sci. USA 86, 1183–1187 (1989).
Koch, C., Schleiffer, A., Ammerer, G. & Nasmyth, K. Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases activate bound transcription factor SBF (Swi4/Swi6) at start, whereas Clb/Cdc28 kinases displace it from the promoter in G2. Genes Dev. 10, 129–141 ( 1996).
Harrington, L. A. & Andrews, B. J. Binding to the yeast Swi4,6-dependent cell cycle box, CACGAAA, is cell cycle regulated in vivo. Nucleic Acids Res. 24, 558– 565 (1996).
Breeden, L. & Mikesell, G. Three independent forms of regulation affect expression of HO, CLN1 and CLN2 during the cell cycle of Saccharomyces cerevisiae. Genetics 138, 1015–1024 (1994).
Chu, S. et al. The transcriptional program of sporulation in budding yeast. Science 282, 699–705 ( 1998).
Johnston, L. H., Johnson, A. L. & Barker, D. G. The expression in meiosis of genes which are transcribed periodically in the mitotic cell cycle of budding yeast. Exp. Cell Res. 165, 541–549 ( 1986).
Dirick, L., Goetsch, L., Ammerer, G. & Byers, B. Regulation of meiotic S phase by Ime2 and a Clb5,6-associated kinase in Saccharomyces cerevisiae . Science 281, 1854– 1857 (1998).
Madhani, H. D., Galitski, T., Lander, E. S. & Fink, G. R. Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signalling mutants. Proc. Natl Acad. Sci. USA 96, 12530–12535 (1999).
Zhu, Y., Takeda, T., Nasmyth, K. & Jones, N. pct1+, which encodes a new DNA-binding partner of p85cdc10, is required for meiosis in the fission yeast Schizosaccharomyces pombe. Genes Dev. 8, 885–898 ( 1994).
Ayté, J., Leis, J. F. & DeCaprio, J. A. The fission yeast protein p73res2 is an essential component of the mitotic MBF complex and a master regulator of meiosis. Mol. Cell. Biol. 17, 6246–6254 (1997).
Leem, S. H., Chung, C. N., Sunwoo, Y. & Araki, H. Meiotic role of SWI6 in Saccharomyces cerevisiae. Nucleic Acids Res. 26, 3154–3158 ( 1998).
DeRisi, J. L., Iyer, V. R. & Brown, P. O. Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278, 680–686 (1997).
Strahl-Bolsinger, S., Hecht, A., Luo, K. & Grunstein, M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev. 11, 83– 93 (1997).
Orlando, V. & Paro, R. Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin. Cell 75, 1187–1198 (1993).
Acknowledgements
We thank J. DeRisi for mapping software; O. Aparacio for immunoprecipitation protocols; A. Khodursky for help with significance tests; and J. Lieb for comments on the manuscript and discussion. This work was supported by grants from the National Institutes of Health, and by the Howard Hughes Medical Institute. P.O.B. is an associate investigator of the Howard Hughes Medical Institute.
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Iyer, V., Horak, C., Scafe, C. et al. Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature 409, 533–538 (2001). https://doi.org/10.1038/35054095
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DOI: https://doi.org/10.1038/35054095
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