The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour supressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins reflecting the marked effects of Runx on cell adhesion.
Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival.
No sample metadata fields
View Samples1507 known genes have been identified differentially regulated during HisOH treatment by more than 2 fold. This includes 250 down-regulated genes and 1257 up-regulated genes.
Expression profiling after activation of amino acid deprivation response in HepG2 human hepatoma cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesEnvironmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesTranscripts (mRNA) during amino acid limitation after MEK was inhibited were analyzed.
A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation.
Cell line, Treatment
View SamplesEnvironmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesPurpose: to identify genes aberrantly expressed upon myocardial ablation of Hif1a Methods: a floxed Hif1a allele was deleted in mouse embryonic hearts using a NXK2.5Cre line. Total RNA was extracted from E12.5 hearts (n=3 for controls and mutants) usinz Trizol and processed for RNA-seq. Reads were mapped to Mm10 reference genome using TopHat2 and Bowtie2. Transcript expression values were determined after transcript normalization with AltAnalyze Results: this analysis revealed a total of 1451 genes significantely (|Fold| > 20% and P<0.05) modulated in Hif1a cKO hearts Overall design: 6 total RNAseq runs with 3 experimental samples and 3 controls samples
HIF1α Represses Cell Stress Pathways to Allow Proliferation of Hypoxic Fetal Cardiomyocytes.
No sample metadata fields
View SamplesPediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST.
Recurrent epimutation of SDHC in gastrointestinal stromal tumors.
No sample metadata fields
View SamplesThe OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11) could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. Importantly, the increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G. We also identified a novel OCT4 downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. This small molecule-based stabilization of synthetic mRNA expression may have multiple applications for future cell-based research and therapeutics.
BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.
Specimen part, Cell line, Treatment
View SamplesIn both beef and dairy cattle, the majority of embryo loss occurs in the first 14-16 days following insemination. During this period, the embryo is completely dependent on its maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to embryo survival.
Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression.
Specimen part
View Samples