The LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of -catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation.
The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation.
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View SamplesPseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression.
The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome.
Sex
View SamplesDepletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that down-regulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after two hours with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We identify genes that mediate this loss of commitment, and show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation. Wild type cells were grown at high Phosphate medium, washed and transferred to no phosphate medium. Sample were taken every 15 minuets for 6 hours Overall design: 25 samples were taken during the time course. Expression data was normalized to the first time point (cells grown at high phosphate medium)
Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
Genetic information, Subject
View SamplesDepletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that down-regulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after two hours with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We identify genes that mediate this loss of commitment, and show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation. Wild type cells were grown at high Phosphate medium, washed and transferred to no phosphate medium. Sample were taken every 15 minuets for 6 hours Overall design: 25 samples were taken during the time course. Expression data was normalized to the first time point (cells grown at high phosphate medium)
Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
Genetic information, Subject
View SamplesDepletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that down-regulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after two hours with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We identify genes that mediate this loss of commitment, and show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation. Wild type cells were grown at high Phosphate medium, washed and transferred to no phosphate medium. Sample were taken every 15 minuets for 6 hours Overall design: 25 samples were taken during the time course. Expression data was normalized to the first time point (cells grown at high phosphate medium)
Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
Genetic information, Subject
View SamplesDepletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that down-regulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after two hours with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We identify genes that mediate this loss of commitment, and show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation. Wild type cells were grown at high Phosphate medium, washed and transferred to no phosphate medium. Sample were taken every 15 minuets for 6 hours Overall design: 25 samples were taken during the time course. Expression data was normalized to the first time point (cells grown at high phosphate medium)
Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
Genetic information, Subject
View SamplesDepletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that down-regulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after two hours with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We identify genes that mediate this loss of commitment, and show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation. Wild type cells were grown at high Phosphate medium, washed and transferred to no phosphate medium. Sample were taken every 15 minuets for 6 hours Overall design: 25 samples were taken during the time course. Expression data was normalized to the first time point (cells grown at high phosphate medium)
Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
Genetic information, Subject
View SamplesDepletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that down-regulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after two hours with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We identify genes that mediate this loss of commitment, and show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation. Wild type cells were grown at high Phosphate medium, washed and transferred to no phosphate medium. Sample were taken every 15 minuets for 6 hours Overall design: 25 samples were taken during the time course. Expression data was normalized to the first time point (cells grown at high phosphate medium)
Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
Genetic information, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis.
Sex, Specimen part
View SamplesA dual platform microarray analysis was used to characterize the temporal transcriptomic response in the mouse liver following trauma and hemmorhagic shock
Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis.
Sex, Specimen part
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