Abstract
Cell-cycle control of transcription seems to be universal, but little is known about its global conservation and biological significance. We report on the genome-wide transcriptional program of the Schizosaccharomyces pombe cell cycle, identifying 407 periodically expressed genes of which 136 show high-amplitude changes. These genes cluster in four major waves of expression. The forkhead protein Sep1p regulates mitotic genes in the first cluster, including Ace2p, which activates transcription in the second cluster during the M-G1 transition and cytokinesis. Other genes in the second cluster, which are required for G1-S progression, are regulated by the MBF complex independently of Sep1p and Ace2p. The third cluster coincides with S phase and a fourth cluster contains genes weakly regulated during G2 phase. Despite conserved cell-cycle transcription factors, differences in regulatory circuits between fission and budding yeasts are evident, revealing evolutionary plasticity of transcriptional control. Periodic transcription of most genes is not conserved between the two yeasts, except for a core set of ∼40 genes that seem to be universally regulated during the eukaryotic cell cycle and may have key roles in cell-cycle progression.
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Acknowledgements
We thank V. Wood and the developers of S. pombe GeneDB for providing this valuable database and for information on orthologs; D. Vetrie, N. Nikdaidou-Katsaridou and A. Ivens for help with microarray printing; I. Hagan and L. Vardy for advice on elutriation; C. Heichinger and M. Hollyoake for help with FACS analyses; M. Sipiczki and B. Morgan for strains; E. Falkenauer and A. Marchand for help with ArrayMiner; S. Watt for technical support; P. Rocca-Serra and E. Holloway for help with ArrayExpress; R. Pettett for developing the gene expression viewer; J. Vilo for help in using SPEXS software and J. Ayté for comments on the manuscript. We apologize to colleagues for not citing all relevant papers because of space constraints; additional references are given in Supplementary Tables 1, 4 and 7 online. This research was supported by Cancer Research UK (P.N. and J.B.) and the European commission TEMBLOR grant (A.B.).
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Supplementary information
Supplementary Fig. 1
Various cell cycle events measured for two synchronized experiments. (PDF 459 kb)
Supplementary Table 1
Genes previously reported as cell cycle regulated. (PDF 199 kb)
Supplementary Table 2
Periodic genes with characterized functions. (PDF 149 kb)
Supplementary Table 3
List of 407 genes periodically expressed during the cell cycle. (PDF 998 kb)
Supplementary Table 4
Enrichment for Gene Ontology (GO) terms among periodically expressed genes. (PDF 107 kb)
Supplementary Table 5
Potential regulatory promoter motifs. (PDF 122 kb)
Supplementary Table 6
Overlap of periodic genes between fission and budding yeasts. (PDF 116 kb)
Supplementary Table 7
S. pombe strains used in this study. (PDF 126 kb)
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Rustici, G., Mata, J., Kivinen, K. et al. Periodic gene expression program of the fission yeast cell cycle. Nat Genet 36, 809–817 (2004). https://doi.org/10.1038/ng1377
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DOI: https://doi.org/10.1038/ng1377
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