Microarray analysis of gene expression during the cell cycle

Cooper, Stephen; Shedden, Kerby

doi:10.1186/1475-9268-2-1

Cited by 47 publications

(6 citation statements)

References 60 publications

(120 reference statements)

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“…Thus, the expected synchronous cell cycle progression was achieved in pooled populations as first described for single cultures [23] . Toxoplasma tachyzoite populations blocked by thymidine and then released satisfy stringent criteria for validating growth synchrony (as defined in Appendix 1 of [24] ). Genomic content of the released populations followed a time-ordered progression permitting nearly two full synchronous divisions before encountering significant host cell lysis (12 h total timeframe, Figs.…”

Section: Resultsmentioning

confidence: 99%

Coordinated Progression through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

et al. 2010

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BackgroundApicomplexan parasites replicate by varied and unusual processes where the typically eukaryotic expansion of cellular components and chromosome cycle are coordinated with the biosynthesis of parasite-specific structures essential for transmission.Methodology/Principal FindingsHere we describe the global cell cycle transcriptome of the tachyzoite stage of Toxoplasma gondii. In dividing tachyzoites, more than a third of the mRNAs exhibit significant cyclical profiles whose timing correlates with biosynthetic events that unfold during daughter parasite formation. These 2,833 mRNAs have a bimodal organization with peak expression occurring in one of two transcriptional waves that are bounded by the transition into S phase and cell cycle exit following cytokinesis. The G1-subtranscriptome is enriched for genes required for basal biosynthetic and metabolic functions, similar to most eukaryotes, while the S/M-subtranscriptome is characterized by the uniquely apicomplexan requirements of parasite maturation, development of specialized organelles, and egress of infectious daughter cells. Two dozen AP2 transcription factors form a series through the tachyzoite cycle with successive sharp peaks of protein expression in the same timeframes as their mRNA patterns, indicating that the mechanisms responsible for the timing of protein delivery might be mediated by AP2 domains with different promoter recognition specificities.Conclusion/SignificanceUnderlying each of the major events in apicomplexan cell cycles, and many more subordinate actions, are dynamic changes in parasite gene expression. The mechanisms responsible for cyclical gene expression timing are likely crucial to the efficiency of parasite replication and may provide new avenues for interfering with parasite growth.

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Section: Resultsmentioning

confidence: 99%

Coordinated Progression through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

et al. 2010

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“…This finding is consistent with the observations that the transcription of many genes is restricted to specific cell cycle phases. 33 In contrast, cells containing transgenes flanked by a MAR maintained consistently elevated levels of the reporter protein. This resulted in a steady-state equilibrium, where a continuous and high rate of synthesis must be compensated by a similar rate of degradation, as dictated by the protein concentration in the cell.…”

Section: Discussionmentioning

confidence: 98%

MAR elements regulate the probability of epigenetic switching between active and inactive gene expression

2009

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Gene expression often cycles between active and inactive states in eukaryotes, yielding variable or noisy gene expression in the short-term, while slow epigenetic changes may lead to silencing or variegated expression. Understanding how cells control these effects will be of paramount importance to construct biological systems with predictable behaviours. Here we find that a human matrix attachment region (MAR) genetic element controls the stability and heritability of gene expression in cell populations. Mathematical modeling indicated that the MAR controls the probability of long-term transitions between active and inactive expression, thus reducing silencing effects and increasing the reactivation of silent genes. Single-cell short-terms assays revealed persistent expression and reduced expression noise in MAR-driven genes, while stochastic burst of expression occurred without this genetic element. The MAR thus confers a more deterministic behavior to an otherwise stochastic process, providing a means towards more reliable expression of engineered genetic systems.

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“…This approach was carried out initially to characterize the yeast cell cycle, and, subsequently, it was applied to examine the cell cycle in multiple organisms (reviewed in ref. 2).…”

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confidence: 99%

Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells

Bar‐Joseph

Siegfried

Brandeis

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

150

191

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Characterization of the transcriptional regulatory network of the normal cell cycle is essential for understanding the perturbations that lead to cancer. However, the complete set of cycling genes in primary cells has not yet been identified. Here, we report the results of genome-wide expression profiling experiments on synchronized primary human foreskin fibroblasts across the cell cycle. Using a combined experimental and computational approach to deconvolve measured expression values into ''single-cell'' expression profiles, we were able to overcome the limitations inherent in synchronizing nontransformed mammalian cells. This allowed us to identify 480 periodically expressed genes in primary human foreskin fibroblasts. Analysis of the reconstructed primary cell profiles and comparison with published expression datasets from synchronized transformed cells reveals a large number of genes that cycle exclusively in primary cells. This conclusion was supported by both bioinformatic analysis and experiments performed on other cell types. We suggest that this approach will help pinpoint genetic elements contributing to normal cell growth and cellular transformation.deconvolution ͉ expression profile T ight regulation of the cell cycle is necessary for the proper growth and development of all organisms. Dysregulation of cell cycle controls leads to proliferative diseases, most notably cancer. One approach to understanding basic cell cycle processes and their deregulation in cancer has been genome-wide characterization of the cell cycle transcriptional program (1). In these microarray experiments, the RNA levels of every gene is measured in a synchronized cell population at multiple time points. Synchronization is achieved by releasing cells from a cell cycle arrest. This approach was carried out initially to characterize the yeast cell cycle, and, subsequently, it was applied to examine the cell cycle in multiple organisms (reviewed in ref. 2).Although arrest methods were effective for characterizing cycling genes in a number of species (3-7), they did not lead to complete synchronization, even for yeast cells (8)(9)(10). A number of methods were introduced for resynchronizing yeast cells by either matching the profiles for the first and second cycle for each gene (9) or by combining expression and bud count information to reconstruct the expression profile (8). These methods were shown to improve (the already good) yeast cell cycle expression data. However, these methods cannot be directly applied to mammalian cells because of two major differences between yeast and mammalian cells: (i) normal diploid mammalian cells lose their synchronization relatively soon after release of growth arrest (11) and (ii) only 50-70% of wild-type mammalian cells reenter the cell cycle after release from arrest (12). The large percentage of arrested cells and loss of synchronization means that expression values represent a mixed population of cells, which introduces high background noise that confounds differentiation between genuine c...

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Microarray analysis of gene expression during the cell cycle

Cited by 47 publications

References 60 publications

Coordinated Progression through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

Coordinated Progression through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

MAR elements regulate the probability of epigenetic switching between active and inactive gene expression

Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells

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