Identification of Cell Cycle-regulated Genes in Fission Yeast (original) (raw)
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Periodic gene expression program of the fission yeast cell cycle
Nature Genetics, 2004
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.
Molecular biology of the cell, 1998
We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures synchronized by three independent methods: alpha factor arrest, elutriation, and arrest of a cdc15 temperature-sensitive mutant. Using periodicity and correlation algorithms, we identified 800 genes that meet an objective minimum criterion for cell cycle regulation. In separate experiments, designed to examine the effects of inducing either the G1 cyclin Cln3p or the B-type cyclin Clb2p, we found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins. Furthermore, we analyzed our set of cell cycle-regulated genes for known and new promoter elements and show that several known elements (or variations thereof) contain information predictive of cell cycle regulation. A full description and complete data sets are available at http://cellcycle-www.stanford...
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.
Genome Research, 1999
Recent developments in genome-wide transcript monitoring have led to a rapid accumulation of data from gene expression studies. Such projects highlight the need for methods to predict the molecular basis of transcriptional coregulation. A microarray project identified the 420 yeast transcripts whose synthesis displays cell cycle-dependent periodicity. We present here a statistical technique we developed to identify the sequence elements that may be responsible for this cell cycle regulation. Because most gene regulatory sites contain a short string of highly conserved nucleotides, any such strings that are involved in gene regulation will occur frequently in the upstream regions of the genes that they regulate, and rarely in the upstream regions of other genes. Our strategy therefore utilizes statistical procedures to identify short oligomers, five or six nucleotides in length, that are over-represented in upstream regions of genes whose expression peaks at the same phase of the cell cycle. We report, with a high level of confidence, that 9 hexamers and 12 pentamers are over-represented in the upstream regions of genes whose expression peaks at the early G 1 , late G 1 , S, G 2 , or M phase of the cell cycle. Some of these sequence elements show a preference for a particular orientation, and others, through a separate statistical test, for a particular position upstream of the ATG start codon. The finding that the majority of the statistically significant sequence elements are located in late G 1 upstream regions correlates with other experiments that identified the late G 1 /early S boundary as a vital cell cycle control point. Our results highlight the importance of MCB, an element implicated previously in late G 1 /early S gene regulation, as most of the late G 1 oligomers contain the MCB sequence or variations thereof. It is striking that most MCB-like sequences localize to a specific region upstream of the ATG start codon. Additional sequences that we have identified may be important for regulation at other phases of the cell cycle.
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.
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.
We previously determined the copy number limits of overexpression for cell division cycle (cdc) regulatory genes in the fission yeast Schizosaccharomyces pombe using the ''genetic tug-of-war'' (gTOW) method. In this study, we measured the levels of tandem affinity purification (TAP)-tagged target proteins when their copy numbers are increased in gTOW. Twenty analyzed genes showed roughly linear correlations between increased protein levels and gene copy numbers, which suggested a general lack of compensation for gene dosage in S. pombe. Cdc16 and Sid2 protein levels but not their mRNA levels were much lower than that expected by their copy numbers, which suggested the existence of a post-transcriptional down regulation of these genes. The cyclin Cig1 protein level and its mRNA level were much higher than that expected by its copy numbers, which suggested a positive feedback mechanism for its expression. A higher Cdc10 protein level and its mRNA level, probably due to cloning its gene into a plasmid, indicated that Cdc10 regulation was more robust than that previously predicted.
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
Current Genetics, 2004
Mechanisms that coordinate cell growth with division are thought to determine the timing of initiation of cell division and to limit overall cell proliferation. To identify genes involved in this process in Saccharomyces cerevisiae, we describe a method that does not rely on cell size alterations or resistance to pheromone. Instead, our approach was based on the cell surface deposition of the Flo1p protein in cells having passed START. We found that over-expression of HXT11 (which encodes a plasma membrane transporter), PPE1 (coding for a protein methyl esterase), or SIK1 (which encodes a protein involved in rRNA processing) shortened the duration of the G1 phase of the cell cycle, prior to the initiation of DNA replication. In addition, we found that, although SIK1 was not part of a mitotic checkpoint, SIK1 over-expression caused spindle orientation defects and sensitized G2/M checkpoint mutant cells. Thus, unlike HXT11 and PPE1, SIK1 over-expression is also associated with mitotic functions. Overall, we used a novel enrichment approach and identified genes that were not previously associated with cell cycle progression. This approach can be extended to other organisms.