Nur77 overexpression in mouse skeletal muscle
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE65585 | GEO | 2015/02/04
SECONDARY ACCESSION(S): PRJNA274417
REPOSITORIES: GEO
Similar Datasets
Project description:We isolated total RNA from gastrocnemius muscle of wildtype and muscle-specific Nur77 overexpressing transgenic mice to identify Nur77-mediated changes in gene expression. Findings confirmed changes in genes involved in carbohydrate metabolism and muscle development. 2 replicate Illumina Single Color Mouse WG-6_V2_0 chips were used. 6 wildtype and 6 transgenic mice overexpressing Nur77 in skeletal muscle were used. RNA was isolated by Trizol and further purified through RNEasy column. RNA from 2 mice were pooled, for a total of 6 samples -- 3 wildtype and 3 transgenic. The same samples were split into two technical replicate chips. Each chip contains 3 wildtype and 3 transgenic samples.
2015-02-04 | E-GEOD-65585 | biostudies-arrayexpress
Project description:The aim was to study the effects of Nur77 on the white adipose tissue transcriptome after fasting. For this purpose we performed gene expression profiling of white adipose tissue from Nur77-/- mice and wildtype (Nur77+/+) littermates submitted to prolonged fasting using microarray analysis on >27k elements cDNA microarrays.
2012-11-09 | E-MEXP-3771 | biostudies-arrayexpress
Project description:Consumption of a protein containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, α-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), that interconverts leucine and α-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wildtype mice were compared using Next Generation RNA-Sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1486/~39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis (eIF2, mTOR, eIF4 and p70S6K pathways including 40S and 60S ribosomal proteins), protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy and cell death) were up-regulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body size, glycemia, plasma insulin, and lipid signaling pathways were observed in BCATm KO mice. Consistently, genes encoding anaerobic and/or oxidative metabolism of carbohydrate, fatty acids and BCAAs were modestly but systematically reduced. Although there was no indication that muscle fiber type was different between KO and wildtype mice, a difference in the abundance of mRNAs associated with a muscular dystrophy phenotype was observed, consistent with the published exercise intolerance of these mice. The results suggest transcriptional adaptations occur in BCATm KO mice that along with altered nutrient signaling may contribute to their previously reported protein turnover, metabolic and exercise phenotypes. Comparison of wildtype and BCATm KO gastrocnemius biological replicates
2015-12-11 | E-GEOD-68915 | biostudies-arrayexpress
Project description:Endogenous changes in the nuclear encoded genes were analysed using RNA-Seq in order to compare the genetic profile of murine CD4 positive T cells isolated from Nur77-deficient mice and their Nur77-competent counterparts.
2018-07-30 | GSE114912 | GEO
Project description:Macrophages exhibit remarkable plasticity in their morphology and mechanics, enabling them to adapt and execute essential inflammatory functions, such as navigating through inflamed tissue and pathogen engulfment. However, the precise regulatory mechanisms governing these dynamic changes in macrophage mechanics during inflammation remain poorly understood. Although the involvement of nuclear receptor Nur77 in macrophage inflammation has been extensively investigated, its potential correlation with cellular mechanics has not been investigated. In this study, we employ cytoskeletal imaging, single-cell acoustic force spectroscopy (AFS), migration and phagocytosis experiments, and RNA-sequencing analysis on bone marrow-derived macrophages (BMDMs) to compare wild-type (WT) and Nur77-deficient (Nur77-KO) cells. Our findings reveal that Nur77-KO BMDMs exhibit changes to their actin networks compared to WT BMDMs, which is associated with a stiffer and more rigid phenotype. Subsequent in-vitro experiments validated our observations, showcasing that Nur77 deficiency leads to enhanced migration, reduced adhesion, and increased phagocytic activity. The transcriptomics data confirmed altered mechanics-related pathways in Nur77-deficient macrophage that are accompanied by a robust pro-inflammatory phenotype. Utilizing previously obtained ChIP-data, we revealed that Nur77 directly targets differentially expressed genes associated with cellular mechanics. In conclusion, while Nur77 is recognized for its role in reducing inflammation of macrophages by inhibiting the expression of pro-inflammatory genes, our study identifies a novel regulatory mechanism where Nur77 governs macrophage inflammation through the modulation of expression of genes involved in cellular mechanics.
2024-08-02 | GSE253423 | GEO
Project description:Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle cells. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved roles for this nuclear receptor in the regulation of nuclear-encoded mitochondrial ribosomal proteins (MRP) and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at MRP gene loci. Nur77 and YY1 co-expression synergistically increases mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.
2024-05-07 | GSE263316 | GEO
Project description:Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle cells. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved roles for this nuclear receptor in the regulation of nuclear-encoded mitochondrial ribosomal proteins (MRP) and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at MRP gene loci. Nur77 and YY1 co-expression synergistically increases mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.
2024-05-07 | GSE263315 | GEO
Project description:To determine the transcriptomic effects of Cpt1b loss on skeletal muscle gene expression, we assessed gastrocnemius muscle in chow-fed control and Cpt1b skeletal muscle specific knockout mice using a serial analysis of gene expression strategy. Complementary bioinformatics pathway enrichment studies were performed which indicated that differentially expressed genes between genotypes were predominantly related to various processes include carbohydrate metabolism, lipid metabolism, amino acid metabolism, cell proliferation, and apoptosis.
2018-11-30 | GSE107138 | GEO
Project description:Nur77 is an orphan member of the nuclear receptor superfamily that is expressed in various types of cells and mediates diverse biological processes. The knock out Nur77 has a mutation in exon 2. Ligands of the nuclear receptor are unknown. Keywords: Dual colour hybridisation on cDNA microarrays, Nur77, Knock out
2007-04-01 | GSE7016 | GEO
Project description:Consumption of a protein containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, α-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), that interconverts leucine and α-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wildtype mice were compared using Next Generation RNA-Sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1486/~39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis (eIF2, mTOR, eIF4 and p70S6K pathways including 40S and 60S ribosomal proteins), protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy and cell death) were up-regulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body size, glycemia, plasma insulin, and lipid signaling pathways were observed in BCATm KO mice. Consistently, genes encoding anaerobic and/or oxidative metabolism of carbohydrate, fatty acids and BCAAs were modestly but systematically reduced. Although there was no indication that muscle fiber type was different between KO and wildtype mice, a difference in the abundance of mRNAs associated with a muscular dystrophy phenotype was observed, consistent with the published exercise intolerance of these mice. The results suggest transcriptional adaptations occur in BCATm KO mice that along with altered nutrient signaling may contribute to their previously reported protein turnover, metabolic and exercise phenotypes.
2015-12-11 | GSE68915 | GEO