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SRP055990
Rattus norvegicus
5 Downloadable Samples
Description
The heart adapts to increased workload through hypertrophic growth of cardiomyocytes. Although beneficial when induced physiologically by exercise, pathological cues including hypertension cause reexpression of fetal genes and dysfunctional hypertrophy, with lasting consequences for cardiac health. We hypothesised that these differences are driven by changes in chromatin-encoded cellular memory. We generated genome-wide maps of transcription and of two stable epigenetic marks, H3K9me2 and H3K27me3, specifically in hypertrophied cardiomyocytes, by selectively flow-sorting their nuclei. This demonstrated a pervasive loss of euchromatic H3K9me2 specifically upon pathological but not physiological hypertrophy, derepressing genes associated with pathological hypertrophy. Levels of the H3K9 methyltransferases, G9a and GLP, were correspondingly reduced. Importantly, pharmacological or genetic inactivation of these enzymes was sufficient to induce pathological hypertrophy and the dedifferentiation associated with it. These findings suggest novel therapeutic opportunities by defining an epigenetic state of cardiomyocytes, acquired during maturation, which is required for maintaining cardiac health. Overall design: Examination of 2 different histone modifications and RNA expression in cardiomyocyte nuclei flow-sorted from hypertrophic rat hearts
Publication Title
The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 69 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Microarray analysis revealed that changes in genes expressions are brain region-dependent; expression of several genes are affected by point mutation L100P, which was verified by RT-PCR (Lcn2, Cyr61, Slc6a12, Slc40a1, Egr2), a few genes are affected by genotype and valproate (Dusp1 and Purb), suggesting their role in valproate-induced benificial effect on sensorimotor gaiting in Disc1-L100P mutant mice. The final conclusion will be drawn after series of RT-PCR confirmation.
Publication Title
Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3.
Sample Metadata Fields
Sex, Specimen part, Compound
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2000
Description
The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A/DDX2 RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of Silvestrol and related compounds. For example, eIF4A promotes T-ALL development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with Silvestrol has powerful therapeutic effects in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5'UTR sequences such as the 12-mer guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and Silvestrol-sensitive transcripts are a number of oncogenes, super-enhancer associated transcription factors, and epigenetic regulators. Hence, the 5'UTRs of selected cancer genes harbour a targetable requirement for the eIF4A RNA helicase. Overall design: Comparison of ribosome-protected RNA for drug treated and DMSO treated KOPT-K1 cell, two replicates of ribosome-protected RNA sequencing and three replicates of RNA-seq.
Publication Title
RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 117 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray technology to profile mRNA expression in the skeletal muscle of normal (NGT), glucose intolerant (IGT) and type 2 diabetic (DM) subjects. Groups were classified using WHO criteria and, importantly, the DM group were free of anti hypoglycaemic medication for one week prior to biopsy.
Publication Title
Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS.
Publication Title
Whole-genome expression profile in zebrafish embryos after chronic exposure to morphine: identification of new genes associated with neuronal function and mu opioid receptor expression.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DNA hypomethylation is an important epigenetic modification found to occur in many different cancer types, leading to the upregulation of previously silenced genes and loss of genomic stability. We previously demonstrated that hypoxia and hypoglycaemia (ischemia), two common micro-environmental changes in solid tumors, decrease DNA methylation through the downregulation of DNMTs in human colorectal cancer cells. Here, we utilized a genome-wide cross-platform approach to identify genes hypomethylated and upregulated by ischemia. Following exposure to hypoxia or hypoglycaemia, methylated DNA from human colorectal cancer cells (HCT116) was immunoprecipitated and analysed with an Affymetrix promoter array. Additionally, RNA was isolated and analysed in parallel with an Affymetrix expression array. Ingenuity pathway analysis software revealed that a significant proportion of the genes hypomethylated and upregulated were involved in cellular movement, including PLAUR and CYR61. A Matrigel invasion assay revealed that indeed HCT116 cells grown in hypoxic or hypoglycaemic conditions have increased mobility capabilities. Confirmation of upregulated expression of cellular movement genes was performed with qPCR. The correlation between ischemia and metastasis is well established in cancer progression, but the molecular mechanisms responsible for this common observation have not been clearly identified. Our novel results suggest that hypoxia and hypoglycaemia may be driving changes in DNA methylation through downregulation of DNMTs. This is the first report to our knowledge that provides an explanation for the increased metastatic potential seen in ischemic cells; i.e. that ischemia could be driving DNA hypomethylation and increasing expression of cellular movement genes.
Publication Title
Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic tendon injuries, also known as tendinopathy, are common among professional and recreational athletes. These injuries result in a significant amount of morbidity and health care expenditure and yet little is known about the molecular mechanism leading to tendinopathy. We have used histological evaluation and molecular profiling to determine the gene expression changes in 23 human patients undergoing surgical procedures for the treatment of chronic tendinopathy. Diseased tendons have altered extracellular matrix, fiber disorientation, increased cellular content and vasculature and the absence of inflammatory cells. Global gene expression profiling identified 1783 transcripts with significant different expression patterns in the diseased tendons. Global pathway analysis further suggests altered expression of extracellular matrix proteins and the lack of an appreciable inflammatory response. We have identified pathways and genes regulated in tendinopathy samples that will help contribute to the understanding of the disease towards the development of novel therapeutics.
Publication Title
Regulation of gene expression in human tendinopathy.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Immunoprecipitation of EGFR from irradiated A549 (ATCC CCL185) cells was performed in order to characterize bound mRNA species with the help of microarray analysis
Publication Title
New roles for nuclear EGFR in regulating the stability and translation of mRNAs associated with VEGF signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples