Bovine leukemia virus (BLV) Tax is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach.
Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis.
Cell line
View SamplesHuman T cell leukemia virus type 1 (HTLV-1) Tax is potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. In this study, a large-scale host cell signaling events related to cellular proliferation were used to identify genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis.
Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis.
Cell line
View SamplesRASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells
Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.
Cell line
View SamplesBackground: Here, the role of a-ketoglutarate (aKG) in the epi-metabolic control of DNA demethylation has been investigated in therapeutically relevant cardiac mesenchymal cells (CMSCs) isolated from controls and type 2 diabetes donors. Methods & results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs). Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high fat diet (HFD), injected with streptozotocin (STZ) or both in combination (STZ-HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of aKG synthesis in D-CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised thymine DNA glycosylase (TDG) and ten eleven translocation protein 1 (TET1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that aKG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatched or 5fC. Accordingly, an exogenous source of aKG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5fC accumulation thus partially mimicking the diabetic epigenetic landscape in cells of non- diabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of aKG-dehydrogenase, increased the aKG level in D- CMSCs and in the heart of HFD mice eliciting DNA demethylation, glucose uptake and insulin response. Conclusions: In this report we established that diabetes may epigenetically modify and compromise function of therapeutically relevant cardiac mesenchymal cells. Restoring the epi-metabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes. Overall design: Human primary cardiac mesenchymal cells (CMSC) from 7 diabetic (D) and 7 non-diabetic (ND) donors were analyzed after few rounds of ex vivo expansion. RNA was isolated and sequenced.
Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation.
Specimen part, Subject
View SamplesMuscle biopsies from biceps and deltoid were taken from 5 patients with FSHD, 5 asymptomatic carriers and 5 normal controls. The genome-wide expression patterns were compared using Affymetrix U133 Plus 2.0 chips.
Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers.
Sex, Age, Specimen part, Disease
View SamplesBisphenol A (BPA), an endocrine-disrupting chemical (EDC), is a well-known, ubiquitous estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we first examined the alterations of in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS).
Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus.
Specimen part
View SamplesPlant diseases induced by fungi are one of the most important limiting factors during pre- and post-harvest food production. For decades, synthetic chemical fungicides have been used to control these diseases, however, increase on worldwide regulatory policies and the demand to reduced their application, have led to search new ecofriendly alternatives such as the biostimulants. Commercial application of yeast as biocontrol, have shown low efficacy compared to synthetic fungicides, mostly due to the limited knowledge of the molecular mechanisms of yeast-induced responses. Interestingly, to date, only two genome-wide transciptomic analysis have been used to characterize the mode of action of biocontrols using the plant model Arabidopsis thaliana, missing, in our point of view, all its molecular and genomic potential. Here we described that compounds released by the biocontrol yeast Hanseniaspora opuntiae (HoFs) can protect Glycine max and Arabidopsis thaliana plants against the broad host-range necrotroph fungi Corynespora cassiicola and Botrytis cinerea, respectively. We show that HoFs have a long-lasting, dose-dependent local and systemic effect against Botrytis cinerea. Additionally, we performed a genome-wide transcriptomic analysis to identified HoFs-induced differentially expressed genes in Arabidopsis thaliana. Importantly, our work provides a novel and valuable information that can help the researchers to improve HoFs efficacy in order to become an ecofriendly alternative to synthetic fungicides Overall design: RNAseq from HOF-treated Arabidopsis thaliana leaves
Compounds Released by the Biocontrol Yeast <i>Hanseniaspora opuntiae</i> Protect Plants Against <i>Corynespora cassiicola</i> and <i>Botrytis cinerea</i>.
Specimen part, Subject
View SamplesPlants possess a cold acclimation system to acquire freezing tolerance through pre-exposure to non-freezing low temperatures. The transcriptional cascade of C-repeat binding factors (CBFs)/dehydration response element-binding factors (DREBs) is considered a major transcriptional regulatory pathway during cold acclimation. However, little is known regarding the functional significance of mRNA stability regulation in the response of gene expression to cold stress. The actual level of individual mRNAs is determined by a balance between mRNA synthesis and degradation. Therefore, it is important to assess the regulatory steps to increase our understanding of gene regulation. Here, we analyzed temporal changes in mRNA amounts and half-lives in response to cold stress in Arabidopsis cell cultures based on genome-wide analysis. In this mRNA decay array method, mRNA half-life measurements and microarray analyses were combined. In addition, temporal changes in the integrated value of transcription rates were estimated from the above two parameters using a mathematical approach. Our results showed that several cold-responsive genes, including Cold-regulated 15a, were relatively destabilized, whereas the mRNA amounts were increased during cold treatment by accelerating the transcription rate to overcome the destabilization. Considering the kinetics of mRNA synthesis and degradation, this apparently contradictory result supports that mRNA destabilization is advantageous for the swift increase in CBF-responsive genes in response to cold stress.
Co-ordinated Regulations of mRNA Synthesis and Decay during Cold Acclimation in Arabidopsis Cells.
Cell line
View SamplesWhile gene regulatory networks involved in cardiogenesis have been characterized, the role of bioenergetics remains less studied. Here we show that until midgestation, myocardial metabolism is compartmentalized, with a glycolytic signature restricted to compact myocardium contrasting with increased mitochondrial oxidative activity in the trabeculae. HIF1a regulation mirrors this pattern, with expression predominating in compact myocardium and scarce in trabeculae. By midgestation, the compact myocardium downregulates HIF1a and switches toward oxidative metabolism. Deletion of the E3 ubiquitin ligase Vhl results in HIF1a hyperactivation, disrupting metabolic compartmentalization and blocking the midgestational shift toward oxidative phosphorylation. Moreover, the altered glycolytic signature induced by HIF1 trabecular activation precludes regulation of genes essential for cardiac conduction system establishment. Our findings reveal VHL-HIF-mediated metabolic compartmentalization in the developing heart and the connection between metabolism and myocardial differentiation. These results highlight the importance of bioenergetics in ventricular myocardium specialization and its potential relevance to congenital heart disease. Overall design: RNA was isolated from individual E12.5 embryonic hearts after removal of the atria and valvular region. KOs and control littermates were matched by somite count, and a total number of 3 KOs and 3 controls from 3 independent litters were used. For RNA extraction, QIAzol Lysis Reagent (Qiagen; CA; USA) and the miRNeasy Mini Kit (Qiagen; CA; USA) were used. RNA was quantified and its purity checked with a NanoDrop ND-1000 spectophotometer (Thermo Scientific; MA; USA). RNA integrity was verified with an Agilent 2100 Bioanalyzer (Agilent Technologies; CA; USA). Index-tagged cDNA libraries were constructed from 500 ng of total RNA using the TruSeq RNA Sample Preparation v2 Kit (Illumina; CA; USA). Libraries were quantified by Quant-iTâ„¢ dsDNA HS assay in a Q-bit fluorometer (Life Technologies; CA; USA). Average library size and size distribution were determined by DNA 1000 assay in an Agilent 2100 Bioanalyzer. Libraries were normalized to 10nM using 10mM Tris-HCl, pH8.5 containing 0.1% Tween 20 and then applied to an Illumina flow cell for cluster generation (True Seq SR Cluster Kit V2 cBot) and sequencing-by-synthesis. Single reads of length 75bp were generated with the TruSeq SBS Kit v5 (Illumina; CA; USA) on the Genome Analyzer IIx platform, following the standard RNA sequencing protocol. Reads were further processed using the CASAVA package (Illumina; CA; USA) to split reads according to adapter indexes and produce fastq files.
Myocardial VHL-HIF Signaling Controls an Embryonic Metabolic Switch Essential for Cardiac Maturation.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line, Treatment
View Samples