scholarly journals Predicting cell-cycle expressed genes identifies canonical and non-canonical regulators of time-specific expression in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Nicholas L Panchy ◽  
John P. Lloyd ◽  
Shin-Han Shiu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Target Genes ◽  
Specific Cell ◽  
Data Sets ◽  
Cell Cycle Regulators ◽  
Specific Expression ◽  
Regulatory Data ◽  
Time Specific ◽  
Cycle Regulation

AbstractThe collection all TFs, target genes and their interactions in an organism form a gene regulatory network (GRN), which underly complex patterns of transcription even in unicellular species. However, identifying which interactions regulate expression in a specific temporal context remains a challenging task. With multiple experimental and computational approaches to characterize GRNs, we predicted general and phase-specific cell-cycle expression in Saccharomyces cerevisiae using four regulatory data sets: chromatin immunoprecipitation (ChIP), TF deletion data (Deletion), protein binding microarrays (PBMs), and position weight matrices (PWMs). Our results indicate that the source of regulatory interaction information significantly impacts our ability to predict cell-cycle expression where the best model was constructed by combining selected TF features from ChIP and Deletion data as well as TF-TF interaction features in the form of feed-forward loops. The TFs that were the best predictors of cell-cycle expression were enriched for known cell-cycle regulators but also include regulators not implicated in cell-cycle regulation previously. In addition, ChIP and Deletion datasets led to the identification different subsets of TFs important for predicting cell-cycle expression. Finally, analysis of important TF-TF interaction features suggests that the GRN regulating cell cycle expression is highly interconnected and clustered around four groups of genes, two of which represent known cell-cycle regulatory complexes, while the other two contain TFs that are not known cell-cycle regulators (Ste12-Tex1 and Rap1-Hap1-Msn4), but are nonetheless important to regulating the timing of expression. Thus, not only do our models accurately reflect what is known about the regulation of the S. cerevisiae cell cycle, they can be used to discover regulatory factors which play a role in controlling expression during the cell cycle as well as other contexts with discrete temporal patterns of expression.

Quantitation of alpha-factor internalization and response during the Saccharomyces cerevisiae cell cycle

1991 ◽  
Vol 11 (10) ◽  
pp. 5251-5258
Author(s):  
B Zanolari ◽  
H Riezman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Surface ◽  
Cell Surface Receptors ◽  
Specific Cell ◽  
Surface Receptors ◽  
Cycle Arrest ◽  
A Cells ◽  
Alpha Factor ◽  
Inducible Genes

The alpha-factor pheromone binds to specific cell surface receptors on Saccharomyces cerevisiae a cells. The pheromone is then internalized, and cell surface receptors are down-regulated. At the same time, a signal is transmitted that causes changes in gene expression and cell cycle arrest. We show that the ability of cells to internalize alpha-factor is constant throughout the cell cycle, a cells are also able to respond to pheromone throughout the cycle even though there is cell cycle modulation of the expression of two pheromone-inducible genes, FUS1 and STE2. Both of these genes are expressed less efficiently near or just after the START point of the cell cycle in response to alpha-factor. For STE2, the basal level of expression is modulated in the same manner.

scholarly journals Posttranslational Phosphorylation and Ubiquitination of the Saccharomyces cerevisiae Poly(A) Polymerase at the S/G2 Stage of the Cell Cycle

2000 ◽  
Vol 20 (8) ◽  
pp. 2794-2802 ◽  
Author(s):  
Neptune Mizrahi ◽  
Claire Moore
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Sorting ◽  
S Phase ◽  
Phase Arrest ◽  
Phosphatase Treatment ◽  
M Phase ◽  
64 Kda Protein ◽  
Mitotic Phosphorylation ◽  
Cycle Regulation

ABSTRACT The poly(A) polymerase of the budding yeast Saccharomyces cerevisiae (Pap1) is a 64-kDa protein essential for the maturation of mRNA. We have found that a modified Pap1 of 90 kDa transiently appears in cells after release from α-factor-induced G1 arrest or from a hydroxyurea-induced S-phase arrest. While a small amount of modification occurs in hydroxyurea-arrested cells, fluorescence-activated cell sorting analysis and microscopic examination of bud formation indicate that the majority of modified enzyme is found at late S/G2 and disappears by the time cells have reached M phase. The reduction of the 90-kDa product upon phosphatase treatment indicates that the altered mobility is due to phosphorylation. A preparation containing primarily the phosphorylated Pap1 has no poly(A) addition activity, but this activity is restored by phosphatase treatment. A portion of Pap1 is also polyubiquitinated concurrent with phosphorylation. However, the bulk of the 64-kDa Pap1 is a stable protein with a half-life of 14 h. The timing, nature, and extent of Pap1 modification in comparison to the mitotic phosphorylation of mammalian poly(A) polymerase suggest an intriguing difference in the cell cycle regulation of this enzyme in yeast and mammalian systems.

scholarly journals Adenomatous Polyposis Coli Loss Controls Cell Cycle Regulators and Response to Paclitaxel

2020 ◽  
Author(s):  
Emily M. Astarita ◽  
Camden A. Hoover ◽  
Sara M. Maloney ◽  
T. Murlidharan Nair ◽  
Jenifer R. Prosperi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Adenomatous Polyposis Coli ◽  
Cyclin B1 ◽  
Cell Cycle Analysis ◽  
Specific Cell ◽  
Breast Cancers ◽  
Cell Cycle Regulators ◽  
Adenomatous Polyposis ◽  
Polyposis Coli

AbstractAdenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in PTX-treated APC shRNA1 cells compared to PTX-treated controls, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations.

Egr-1 Maintains NSC Proliferation and Its Overexpression Counteracts Cell Cycle Exit Triggered by the Withdrawal of Epidermal Growth Factor

2018 ◽  
Vol 40 (3) ◽  
pp. 223-233 ◽  
Author(s):  
Arcangela Anna Cera ◽  
Emanuele Cacci ◽  
Camilla Toselli ◽  
Silvia Cardarelli ◽  
Alessandra Bernardi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Target Genes ◽  
Kinase Inhibitors ◽  
Mammalian Brain ◽  
Cell Cycle Regulators ◽  
Egfr Signaling Pathway ◽  
Proliferation And Differentiation ◽  
Adult Nscs ◽  
Extracellular Stimuli

In adult mammals, neural stem cells (NSCs) reside in specialized niches at the level of selected CNS regions, such as the subventricular zone (SVZ). The signaling pathways that reg­ulate NSC proliferation and differentiation remain poorly understood. Early growth response protein 1 (Egr-1) is an important transcription factor, widely studied in the adult mammalian brain, mediating the activation of target genes by a variety of extracellular stimuli. In our study, we aimed at testing how Egr-1 regulates adult NSCs derived from mouse SVZ and, in particular, the interplay between Egr-1 and the proliferative factor EGF. We demonstrate that Egr-1 expression in NSCs is induced by growth factor stimulation, and its level decreases after EGF deprivation or by using AG1478, an inhibitor of the EGF/EGFR signaling pathway. We also show that Egr-1 overexpression rescues the cell proliferation decrease observed either after EGF removal or upon treatment with AG1478, suggesting that Egr-1 works downstream of the EGF pathway. To better understand this mechanism, we investigated targets downstream of both the EGF pathway and Egr-1, and found that they regulate genes involved in NSC proliferation, such as cell cycle regulators, cyclins, and cyclin-dependent kinase inhibitors.

scholarly journals Preclinical Perspectives on Garlic and Cancer

2006 ◽  
Vol 136 (3) ◽  
pp. 827S-831S ◽  
Author(s):  
John A. Milner
Keyword(s):  
Cell Cycle ◽  
Redox Status ◽  
Sulfur Compounds ◽  
Specific Cell ◽  
Organosulfur Compounds ◽  
Anticancer Properties ◽  
Cellular Events ◽  
Histone Hyperacetylation ◽  
Chemically Induced ◽  
Cycle Regulation

ABSTRACT Evidence continues to point to the anticancer properties of fresh garlic extracts, aged garlic, garlic oil, and a number of specific organosulfur compounds generated by processing garlic. These anticarcinogenic and antitumorigenic characteristics appear to arise through both dose- and temporal-related changes in a number of cellular events involved with the cancer process, including those involving drug metabolism, immunocompetence, cell cycle regulation, apoptosis, and angiogenesis. The ability of garlic and related allyl sulfur compounds to block tumors in the colon, lung, breast, and liver suggests general mechanisms that are not tissue specific. Whereas relatively few studies have compared the relative efficacy of water- and lipid-soluble allyl sulfur compounds, those that have when using chemically induced carcinogen models suggest little difference in response, whereas tumor proliferation/apoptosis is highly dependent on the species provided. A shift in sulfhydryl groups, alterations in glutathione:oxidized glutathione ratios, and resultant changes in cellular redox status may be involved in some of the phenotypic changes caused by allyl sulfur compounds. Such changes in thiols by allyl sulfurs may also account for the observed hyperphosphorylation of specific cell cycle proteins and the histone hyperacetylation that has been correlated with suppressed tumor cell proliferation. Whereas the anticarcinogenic and antitumorigenic data to date are impressive, additional studies are needed with more modest exposure to allyl sulfur compounds over prolonged periods. Likewise, additional studies are needed that incorporate transgenic and knockout models to assist in the identification of molecular targets for garlic and its associated allyl sulfur components.

scholarly journals Involvement of calcineurin‐dependent degradation of Yap1p in Ca 2+ ‐induced G 2 cell‐cycle regulation in Saccharomyces cerevisiae

EMBO Reports ◽  
2006 ◽  
Vol 7 (5) ◽  
pp. 519-524 ◽  
Author(s):  
Hiroshi Yokoyama ◽  
Masaki Mizunuma ◽  
Michiyo Okamoto ◽  
Josuke Yamamoto ◽  
Dai Hirata ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cycle Regulation

scholarly journals Involvement of S-adenosylmethionine in G1 cell-cycle regulation in Saccharomyces cerevisiae

2004 ◽  
Vol 101 (16) ◽  
pp. 6086-6091 ◽  
Author(s):  
M. Mizunuma ◽  
K. Miyamura ◽  
D. Hirata ◽  
H. Yokoyama ◽  
T. Miyakawa
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cycle Regulation

Novel insights into cardiac regeneration based on differential fetal and adult ovine heart transcriptomic analysis

2020 ◽  
Vol 318 (4) ◽  
pp. H994-H1007
Author(s):  
Paola Locatelli ◽  
Mariano N. Belaich ◽  
Ayelén E. López ◽  
Fernanda D. Olea ◽  
Martín Uranga Vega ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Differentially Expressed Gene ◽  
Cardiac Regeneration ◽  
Differentially Expressed ◽  
Cell Cycle Regulators ◽  
Large Mammal ◽  
Adult Sheep ◽  
Laboratory Rodents ◽  
Cycle Regulation

The adult mammalian cardiomyocyte has a very limited capacity to reenter the cell cycle and advance into mitosis. Therefore, diseases characterized by lost contractile tissue usually evolve into myocardial remodeling and heart failure. Analyzing the cardiac transcriptome at different developmental stages in a large mammal closer to the human than laboratory rodents may serve to disclose positive and negative cardiomyocyte cell cycle regulators potentially targetable to induce cardiac regeneration in the clinical setting. Thus we aimed at characterizing the transcriptomic profiles of the early fetal, late fetal, and adult sheep heart by employing RNA-seq technique and bioinformatic analysis to detect protein-encoding genes that in some of the stages were turned off, turned on, or differentially expressed. Genes earlier proposed as positive cell cycle regulators such as cyclin A, cdk2, meis2, meis3, and PCNA showed higher expression in fetal hearts and lower in AH, as expected. In contrast, genes previously proposed as cell cycle inhibitors, such as meis1, p16, and sav1, tended to be higher in fetal than in adult hearts, suggesting that these genes are involved in cell processes other than cell cycle regulation. Additionally, we described Gene Ontology (GO) enrichment of different sets of genes. GO analysis revealed that differentially expressed gene sets were mainly associated with metabolic and cellular processes. The cell cycle-related genes fam64a, cdc20, and cdk1, and the metabolism-related genes pitx and adipoq showed strong differential expression between fetal and adult hearts, thus being potent candidates to be targeted in human cardiac regeneration strategies. NEW & NOTEWORTHY We characterized the transcriptomic profiles of the fetal and adult sheep hearts employing RNAseq technique and bioinformatic analyses to provide sets of transcripts whose variation in expression level may link them to a specific role in cell cycle regulation. It is important to remark that this study was performed in a large mammal closer to humans than laboratory rodents. In consequence, the results can be used for further translational studies in cardiac regeneration.

scholarly journals Comprehensive Identification of Cell Cycle–regulated Genes of the YeastSaccharomyces cerevisiaeby Microarray Hybridization

1998 ◽  
Vol 9 (12) ◽  
pp. 3273-3297 ◽  
Author(s):  
Paul T. Spellman ◽  
Gavin Sherlock ◽  
Michael Q. Zhang ◽  
Vishwanath R. Iyer ◽  
Kirk Anders ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Dna Microarrays ◽  
Full Description ◽  
Temperature Sensitive ◽  
Data Sets ◽  
Mrna Levels ◽  
Yeast Cultures ◽  
Yeast Genes ◽  
Cycle Regulation

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: α 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.edu

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