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Role of estrogen related receptor alpha (ERRa) in CD4+ T cell gene expression

ABSTRACT: ERRa is an orphan nuclear receptor with an established role in cell metabolism. Our studies demonstrate that acute or chronic loss of ERRa broadly affects mitochondrial and glycolytic metabolism in CD4+ T cells and results in diminished T cell function and differentation. In this array, we assessed the contribution of ERRa to changes in gene expression in resting and stimulated CD4+ T cells with the goal of identifying specific metabolic genes that exhibit altered expression in the presence or absence of ERRa. Please see related publication: Michalek, et al. PNAS 2011.

ORGANISM(S): Mus musculus

PROVIDER: GSE33108 | GEO | 2011/10/21

SECONDARY ACCESSION(S): PRJNA149499

REPOSITORIES: GEO

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Role of estrogen related receptor alpha (ERRa) in CD4+ T cell gene expression

Project description:ERRa is an orphan nuclear receptor with an established role in cell metabolism. Our studies demonstrate that acute or chronic loss of ERRa broadly affects mitochondrial and glycolytic metabolism in CD4+ T cells and results in diminished T cell function and differentation. In this array, we assessed the contribution of ERRa to changes in gene expression in resting and stimulated CD4+ T cells with the goal of identifying specific metabolic genes that exhibit altered expression in the presence or absence of ERRa. Please see related publication: Michalek, et al. PNAS 2011. CD4+ T cells from 6-8 week old mice were negatively selected (Miltenyi), resulting in >95% purity and cultured in RPMI 1640 (Mediatech) with 10% FBS (Gemini Bio-Products). Wild-type (WT) and ERRa−/− (ERRKO) CD4+ T cells were harvested directly ex vivo or stimulated with anti-CD3 and anti-CD28 antibodies for 12 h in the presence or absence of the pharmacological inhibtors of ERRa XCT790 and Compound A. RNA was harvested using the RNeasy Plus kit from Qiagen.The microarray was prepared and analyzed by the Duke Microarray Facility using Ambion Message Amp Premier labeling and Affymetrix GeneChip Mouse Genome 430A 2.0. Each assay contains three independent biologic replicates.

2011-10-20 | E-GEOD-33108 | biostudies-arrayexpress

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Project description:To determine the role of estrogen-related receptor alpha and gamma (ERRa/g) on chromatin accessibility, we performed ATAC-seq studies with WT control and ERRa/g KO hiPSC-CMs. We found that ERRa/g activates cardiac chromatin accessibilities in hiPSC-CMs. A subset of the decreased ATAC signals by loss of ERRa/g overlapped ERRg peaks (GSE113760) in hiPSC-CMs, suggesting that ERRg might be directly involved in the activation of cardiac chromatin accessibilities. The motif analysis with decreased ATAC signal by loss of ERRa/g revealed that cardiac-enriched transcription factors such as MEF2 and GATA could cooperate with ERR.

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RNA-Seq transcriptome profiling of postnatal age 35 days or P35 ventricles of cardiac-specific estrogen-related receptor alpha and gamma (ERRa/g) knock down (KD) mouse generated by AAV-cTnT-Cre injection and its control AAV-Luc injection.

Project description:Transcriptional regulatory circuits that drive cardiomyocyte maturation during the developmental process are poorly understood. Estrogen-related receptor alpha and gamma (ERRa/g) have been shown to be involved in all aspects of mitochondrial energy production. However, the function of ERR during the postnatal cardiac developmental process is unclear. To examine the role of (ERRa/g) during postnatal cardiac maturation, we generated inducible cardiac-specific ERRa/g knockdown (KD) mice with adeno-associated virus serotype 9 (AAV9) expressing Cre. We found that at P35 a number of genes involved in oxidative mitochondrial metabolism including OXPHOS, TCA cycle, branched chain amino acid catabolism, and fatty acid oxidation were dramatically downregulated. Also, the KD hearts exhibited a significant downregulation of adult cardiac contractile protein, ion channel and Ca2+ handling genes. In contrast, fetal cardiac genes and non-cardiac genes that express in fibroblast or skeletal muscle cells were ectopically induced in the KD hearts. These results suggest that ERRa/g are essential factors for the broad postnatal cardiomyocyte maturation program.

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Differential gene expression between ERRa KO and WT mouse kidneys

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