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GSE46545
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes.
Publication Title
The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes. Overall design: RNA-seq has been perform in triplicate on mES cell (TT2 : Wildtype, and KO G9a-/-)
Publication Title
The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Fibro-adipogenic progenitors (FAPs) are emerging cellular components of the skeletal muscle regenerative environment. The alternative functional phenotype of FAPs - either supportive of muscle regeneration or promoting fibro-adipogenic degeneration - is a key determinant in the pathogenesis of muscular diseases, including Duchenne Muscular Dystrophy (DMD). However, the molecular regulation of FAPs is still unknown. We show here that an "HDAC-myomiR-BAF60 variant network" regulates the functional phenotype of FAPs in dystrophic muscles of mdx mice. Combinatorial analysis of gene expression microarray and genome-wide chromatin remodeling by Nuclease accessibility (NA)-seq revealed that HDAC inhibitors de-repress a "latent" myogenic program in FAPs from dystrophic muscles at early stages of disease progression. In these cells HDAC inhibition promoted the expression of two core components of the myogenic transcriptional machinery, MyoD and BAF60C, and upregulated the myomiRs (miRs) miR-1.2, miR-133 and miR-206, which target two alternative BAF60 variants (BAF60A and B) ultimately leading to the activation of a pro-myogenic program at the expense of the fibro-adipogenic phenotype. By contrast, FAPs from dystrophic muscles at late stages of disease progression displayed resistance to HDACi-induced chromatin remodeling at myogenic loci and fail to activate the pro-myogenic phenotype. These results reveal a previously unappreciated disease stage-specific bipotency of mesenchimal cells within the regenerative environment of dystrophic muscles. Resolution of such bi-potency by epigenetic interventions, such as HDACi, provides the molecular rationale for the in situ reprogramming of target cells to promote therapeutic regeneration of dystrophic muscles. Overall design: miRNA modulation upon Histone Deacetylase inhibition in Fibro-Adipogenic Progenitors (FAPs) derived from young mdx mice was evaluated by small RNA-sequencing in 2 controls and 2 treated samples
Publication Title
HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 89 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Strain differences in gene expression in the hypothalamus of BXD recombinant inbred mice
Publication Title
Sex-specific modulation of gene expression networks in murine hypothalamus.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Identification of genes differentially expressed in roots of Arabidopsis Col-0 and ndr1-1 mutants 48 h post inoculation with the fungal pathogen Verticillium longisporum.
Publication Title
Susceptibility to Verticillium longisporum is linked to monoterpene production by TPS23/27 in Arabidopsis.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Establishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that indomethacin and nimesulide influence expression of some genes among which are those coding for enzymes required for synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of indomethacin and nimesulide at the molecular level in terms of modulation of gene expression by these substances.
Publication Title
Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of patients taking statins experience muscle related adverse events. Myalgia, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels, is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin-associated myalgia are not clearly understood. To elucidate changes in gene expression associated with statin-induced myalgia, we compared profiles of gene expression in the biopsied skeletal muscle from statin-intolerant patients undergoing statin re-challenge versus those of statin-tolerant controls. A robust separation of statin-intolerant and statin-tolerant cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of statin intolerant patients, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals are genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario further bolstered by the discovery that a number of single nucleotide polymorphisms (e.g., SLCO1B1, SLCO2B1 and RYR2) associated with statin myopathy were observed with increased frequency among statin-intolerant study subjects.
Publication Title
Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Establishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that genistein influences expression of some genes among which are those coding for enzymes required for synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of genistein at the molecular level in terms of modulation of gene expression by this substance.
Publication Title
The phytoestrogen genistein modulates lysosomal metabolism and transcription factor EB (TFEB) activation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Establishment of a transcriptomic profile of human cells treated with kaemferol, daidzein, kaemferol/genistein, or daidzein/genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein influence expression of some genes, among which are those coding for enzymes required for the synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein at the molecular level in terms of modulation of gene expression.
Publication Title
Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples