The epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CBP, a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Morphological and behavioral analyses demonstrated that EE ameliorates deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-enhanced spatial navigation and patter separation ability. These defects correlated with an attenuation of the transcriptional program induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics.
CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
Sex, Age, Specimen part
View SamplesCyanide is stoichiometrically produced as a co-product of the ethylene biosynthesis pathway, and it is detoxified by the b-cyanoalanine synthase enzyme. The molecular and phenotypical analysis of T-DNA insertional mutants of the mitochondrial b-cyanoalanine synthase CYS-C1 suggests that discrete accumulation of cyanide is not toxic for the plant and does not alter mitochondrial respiration rates, but does act as a strong inhibitor of root hair development. The cys-c1 null allele is defective in root hair formation and accumulates cyanide in root tissues. The root hair defect is phenocopied in wild type plants by the exogenous addition of cyanide to the growth medium and is reversed by the addition of hydroxocobalamin. Hydroxocobalamin not only recovers the root phenotype of the mutant, but also the formation of ROS at the initial step of the root hair tip. Transcriptional profile analysis of the cys-c1 mutant reveals that cyanide accumulation acts as a repressor signal for several genes encoding enzymes involved in cell wall rebuilding and the formation of the root hair tip, as well as genes involved in ethylene signaling and metabolism. Our results demonstrate that mitochondrial b-cyanoalanine synthase activity is essential to maintain a low level of cyanide for proper root hair development.
Mitochondrial beta-cyanoalanine synthase is essential for root hair formation in Arabidopsis thaliana.
Specimen part
View SamplesGene expression from Wild-type and NFAT5 knock-out Mouse Embryonic Fibroblasts
Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below. Purpose: Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) causes several lymphoproliferative disorders, including KS, a common AIDS-associated malignancy. Cellular and viral microRNAs (miRNAs) have been shown to play important roles in regulating the expression of genes in oncogenesis. Herpesviruses, including KSHV, encode for miRNAs that are involved in angiogenesis, inflammation and apoptosis. A better knowledge of the miRNA-mediated pathways that regulate KSHV infection is therefore essential for an improved understanding of viral infection and pathogenesis. Methods: In this study, we used deep sequencing to analyze miRNA, both viral and human, and mRNA expression in KS tumor-derived human cells. Results: This approach revealed 153 differentially expressed human miRNAs between KSHV-positive and -negative cells. Differential expression of eight miRNAs was independently confirmed by qRT-PCR. We additionally showed that a majority (~73%) of KSHV-regulated miRNAs are down-regulated, including most members of the 14q32 miRNA cluster. Specifically, human miR-409-3p, which is known to target the pro-angiogenic growth factor angiogenin and the inflammation marker fibrinogen-beta, was significantly down-regulated in KSHV-infected cells based on deep sequencing and qRT-PCR. Despite this substantial down-regulation of cellular miRNAs, hsa-miR-708-5p was significantly up-regulated by KSHV and has been shown to directly inhibit pro-apoptotic protease Caspase-2. Finally, we evaluated to what extent there was an inverse correlation between miRNA and mRNA expression levels. Using filtered datasets, we identified relevant canonical pathways that were significantly enriched. Conclusion: Taken together, our data demonstrate that most human miRNAs affected by KSHV are repressed and our findings highlight the relevance of studying the post-transcriptional gene regulation of miRNAs for KSHV-associated malignancies. Overall design: Refer to individual Series. 6 samples analyzed (one cell type). Two experimental conditions: uninfected vs. chronically KSHV-infected cells (n=3). Two sequencing platforms: microRNA-Seq and mRNA-Seq.
Next-Generation Sequencing Analysis Reveals Differential Expression Profiles of MiRNA-mRNA Target Pairs in KSHV-Infected Cells.
No sample metadata fields
View SamplesGlobal gene expression analysis of grapevine cv. Pinot Noir berries during development and ripening. Time-course comparison of samples collected at three developmental stages (stages 33, 34 and 36 according to the modified E-L system, ref: Coombe BG, Aust J Grape Wine Res 1995, 1: 104-110) during three seasons (2003, 2005 and 2006).
Genome-wide transcriptional analysis of grapevine berry ripening reveals a set of genes similarly modulated during three seasons and the occurrence of an oxidative burst at vèraison.
Age, Specimen part, Time
View SamplesGlobal gene expression analysis of grapevine cv. Pinot Noir berries during development and ripening. Time-course comparison of samples collected at three developmental stages (stages 33, 34 and 36 according to the modified E-L system, ref: Coombe BG, Aust J Grape Wine Res 1995, 1: 104-110) during three seasons (2003, 2005 and 2006). Data for each of the three seasons were normalized independently within each season, using gcRMA.
Genome-wide transcriptional analysis of grapevine berry ripening reveals a set of genes similarly modulated during three seasons and the occurrence of an oxidative burst at vèraison.
Specimen part
View SamplesAnaplastic large-cell lymphoma (ALCL) makes up approximately 15% of paediatric non-Hodgkin's lymphomas of childhood. The vast majority of them is associated with the t(2;5)(p23;q35) translocation that results in the expression of a hybrid oncogenic tyrosine kinase, NPM-ALK. In order to investigate ALCL biological characteristics we used transcriptional profiling approach. Genome-wide gene expression profiling, performed on 23 paediatric ALCL and 12 reactive lymph nodes specimens, showed two novel ALCL subgroups based on their NPM-ALK expression levels (named (ALK low and ALK high). Gene set enrichment analysis revealed, in ALK low samples, a positive enrichment of genes involved in the Interleukin signaling pathway, whereas we found increased expression of genes related to cell cycle progression and division in ALK high tumour samples, such as Aurora Kinase A (AURKA) and B (AURKB). Growth inhibition was observed upon administration of AURKA and AURKB inhibitors Alisertib and Barasertib and it was associated with perturbation of the cell cycle and induction of apoptosis. In conclusion we identified two novel ALCL subgroups, which display unique biological characteristics suggesting sensitivity to distinct targeted therapies.
NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma.
No sample metadata fields
View SamplesExisting controversy regarding the importance of AMP-activated protein kinase (AMPK) in fatty acid (FA) oxidation in skeletal muscle with contraction/exercise may to some extent pertain to redundant AMPK1 signaling. Using a mouse model lacking both AMPK1 and -2 in skeletal muscle specifically (mdKO) we hypothesized that FA utilization would be impaired in skeletal muscle. Calorimetric analysis showed a similar respiratory exchange ratio (RER) of AMPK WT and mdKO mice when fed normal chow, a high fat diet or with prolonged fasting. Though, in vivo treadmill exercise at the same relative intensity induced a higher RER in mdKO mice compared to WT (WT=0.81; mdKO=0.87; p<0.01) indicating a decreased utilization of FA. Ex vivo incubation of soleus muscle revealed that basal and contraction-induced FA oxidation was impaired in mdKO mice, suggesting that the increased RER during in vivo running exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 and FABPpm (by 17-40%) together with abolishment of TBC1D1 Ser237 phosphorylation in mdKO mice, may result in lower FA transport capacity and FA transport protein translocation to sarcolemma, respectively. In summary this study shows that the catalytically active AMPK subunits are required for normal stimulation of FA utilization during exercise and contractions.
AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.
Specimen part
View SamplesRNA-sequencing from Aclyf/f and Acly-/- preadipocytes generated from Aclyf/f mice and induced to differentiate to adipocytes. Overall design: Examination of gene expression during adipocyte differentiation, with Acly intact or deleted
Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females.
Specimen part, Cell line, Subject, Time
View SamplesWe used Affymetrix HG U133 Plus 2.0 GeneChips to compare the transcriptome of miR-145-overexpressing MDA-MB-231 cells against negative control miRNA precursor-transfected cells.
miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness.
Specimen part
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