Periodic gene expression program of the fission yeast cell cycle (original) (raw)
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Cell-Cycle Control of Gene Expression in Budding and Fission Yeast
Annual Review of Genetics, 2005
Cell-cycle control of transcription seems to be a universal feature of proliferating cells, although relatively little is known about its biological significance and conservation between organisms. The two distantly related yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have provided valuable complementary insight into the regulation of periodic transcription as a function of the cell cycle. More recently, genome-wide studies of proliferating cells have identified hundreds of periodically expressed genes and underlying mechanisms of transcriptional control. This review discusses the regulation of three major transcriptional waves, which roughly coincide with three main cell-cycle transitions (initiation of DNA replication, entry into mitosis, and exit from mitosis). I also compare and contrast the transcriptional regulatory networks between the two yeasts and discuss the evolutionary conservation and possible roles for cell cycle-regulated transcription.
Identification of Cell Cycle-regulated Genes in Fission Yeast
Molecular Biology of the Cell, 2005
Cell cycle progression is both regulated and accompanied by periodic changes in the expression levels of a large number of genes. To investigate cell cycle-regulated transcriptional programs in the fission yeast Schizosaccharomyces pombe, we developed a whole-genome oligonucleotide-based DNA microarray. Microarray analysis of both wild-type and cdc25 mutant cell cultures was performed to identify transcripts whose levels oscillated during the cell cycle. Using an unsupervised algorithm, we identified 747 genes that met the criteria for cell cycle-regulated expression. Peaks of gene expression were found to be distributed throughout the entire cell cycle. Furthermore, we found that four promoter motifs exhibited strong association with cell cycle phase-specific expression. Examination of the regulation of MCB motif-containing genes through the perturbation of DNA synthesis control/MCB-binding factor (DSC/MBF)-mediated transcription in arrested synchronous cdc10 mutant cell cultures r...
BMC Systems Biology, 2009
Background: Fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae are among the original model organisms in the study of the cell-division cycle. Unlike budding yeast, no large-scale regulatory network has been constructed for fission yeast. It has only been partially characterized. As a result, important regulatory cascades in budding yeast have no known or complete counterpart in fission yeast.
Transcription during meiosis in the fission yeast Schizosaccharomyces pombe
2004
The meiotic cell cycle is the process by which diploid organisms divide to produce haploid gametes and consists of one round of DNA replication followed by two successive nuclear divisions. In the fission yeast, Schizosaccharomyces pombe, meiosis is initiated from G1 phase and involves a complex series of cellular events that lead to the production of four haploid ascospores. The periodic regulation of gene expression is an important mechanism of control of both mitotic- and meiotic-cell-cycle progression. During the mitotic cell cycle of fission yeast a number of genes, including cdc22+, cdc18+ and cdt1+, are expressed specifically at the G1-S phase boundary. These genes are known to be under the control of MCB (MluI cell-cycle box) upstream-activating-sequence motifs and the MBF (MCB binding factor; also known as DSC1) complex. Here we show that control of gene expression during pre-meiotic G1-S-phase is mediated by an MBF-related transcription-factor complex acting upon similar M...
Serial Regulation of Transcriptional Regulators in the Yeast Cell Cycle
Cell, 2001
the end of M and early G1. It is not yet clear whether this model, developed using a small set of genes, will Nine Cambridge Center Cambridge, Massachusetts 02142 extrapolate to regulation of all cell cycle genes. Microarray analysis has revealed that the expression levels of approximately 800 genes vary in a periodic fashion during the yeast cell cycle (Cho et al., 1998; Spellman et al., 1998), but little is known about the regulation of most of these genes. The set of genes controlled 200 Technology Square Cambridge, Massachusetts 02139 by MBF and SBF has recently been identified by using a genome-wide binding method, confirming that these factors are largely bound to genes expressed in late G1 and revealing how sets of functionally related genes are Summary regulated during this time (Iyer et al., 2001). Identification of the genes regulated by all nine transcription factors Genome-wide location analysis was used to determine how the yeast cell cycle gene expression program is
Comprehensive Identification of Cell Cycle-regulated Genes of the Yeast Saccharomyces cerevisiae by
2000
Biology 3273 tion of 2% (wt/vol). Cells from this culture were harvested every 10 min for 40 min for RNA. The entire control culture was harvested at Cell Cycle-regulated Genes in Yeast Vol. 9, December 1998 3275 Figure 4. The S and M clusters. The transcription profiles are displayed as described in the legend to Figure 1. (A) Histone cluster. The eight genes encoding histones and the yeast histone H1 homologue cluster very tightly and are expressed during S phase of the yeast cell cycle. (B) MET cluster. The expression of many of the members of the methionine pathway peaks just after the histones. (C) CLB2 cluster. A subcluster of genes that are expressed similarly to CLB2 highlights genes that peak during M phase.
Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico
Molecular Systems Biology, 2011
Cellular systems are generally robust against fluctuations of intracellular parameters such as gene expression level. However, little is known about expression limits of genes required to halt cellular systems. In this study, using the fission yeast Schizosaccharomyces pombe, we developed a genetic 'tug-of-war' (gTOW) method to assess the overexpression limit of certain genes. Using gTOW, we determined copy number limits for 31 cell-cycle regulators; the limits varied from 1 to 4100. Comparison with orthologs of the budding yeast Saccharomyces cerevisiae suggested the presence of a conserved fragile core in the eukaryotic cell cycle. Robustness profiles of networks regulating cytokinesis in both yeasts (septation-initiation network (SIN) and mitotic exit network (MEN)) were quite different, probably reflecting differences in their physiologic functions. Fragility in the regulation of GTPase spg1 was due to dosage imbalance against GTPase-activating protein (GAP) byr4. Using the gTOW data, we modified a mathematical model and successfully reproduced the robustness of the S. pombe cell cycle with the model.
Evolution of genome-wide gene regulation in the budding yeast cell-division cycle
Genome-wide regulation of gene expression involves a dynamic epigenetic structure which generates an organism's life-cycle. Although changes in gene expression during development have broad effects on many basic phenomena including cell growth, differentiation, morphogenesis, and disease progression, the evolutionary forces influencing gene expression dynamics and gene regulation remain largely unknown, due to the nature of gene expression as a polygenic, quantitative trait. Moreover, gene expression is regulated differentially over time, so evolutionary forces may be influenced by developmental context. To advance the understanding of evolution in the context of the life-cycle, the architecture of gene expression timing control and its influence on expression dynamics must be revealed. This dissertation presents two experimental investigations of the evolution of genes and related structural regions and time-dependent gene expression, using the budding yeasts Saccharomyces cerevisiae and Saccharomyces paradoxus and their mitotic celldivision cycle as model organism and life-cycle. Comparative methodologies were employed to analyze genome-wide patterns of genetic and phenotypic diversity within and between species. Analysis of several dozen yeast genomes reveals a dominant evolutionary mode of purifying selection. Despite limited genetic variability, differences in transcriptional regulation appear to contribute predominantly to interspecies divergence, and altered post-transcriptional regulation of ribosomal genes may have altered the timing of each species' transition from vegetative growth to reproduction, a classic life-history trait. In addition, natural variation in genome-wide gene expression was measured as a time-series through the mitotic cell-division cycle of 10 yeast lines, including one outgroup species. Despite levels of variation consistent with strong stabilizing selection, transcriptome coexpression dynamics have diverged significantly within and between species. A model involving timing pattern changes explains 61% of the between-genome variation in expression dynamics, suggesting that the major mode of transcriptome evolution involves changes in timing (heterochrony) rather than changes in levels (heterometry) of expression. Analysis of heterochrony patterns suggests that timing control is organized into distinct and dynamically-autonomous modules. Divergence in expression dynamics may be explained by pleiotropic changes in modular timing control. Genome-wide gene regulation may utilize a general architecture comprised of multiple discrete event timelines, whose superposition could produce combinatorial complexity in timing patterns.