Differential gene expression between ERRa KO and WT mouse kidneys
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE16623 | GEO | 2010/04/11
SECONDARY ACCESSION(S): PRJNA116267
REPOSITORIES: GEO
Similar Datasets
Project description:Estrogen-related receptor (ERR) alpha is an orphan nuclear receptor highly expressed in the kidneys. ERRalpha is implicated in renal sodium and potassium homeostasis and blood pressure regulation. We used microarray analysis to identify differentially expressed genes in ERR alpha knockout mice kidneys versus wild-type. The results provide insight on the roles of ERRalpha in the kidney. Three biological replicates of WT and ERRaKO were performed, for a total of 6 samples. 2-3 month old males of each genotype were used.
2010-04-11 | E-GEOD-16623 | biostudies-arrayexpress
Project description:PGC-1 transcription factor was customized to limit its interations to ERRalpha. This mutant (2x9) was used to dissect the transcription activation patterns that are attributable to the PGC1-ERR interaction and PGC-1 actions that are independent of ERR. Inactive mutant with the deleted LLXXL motifs (L2L3) and wt PGC-1 were used as negative and positive controls respectively. BGAL-expressing construct was used to control for non-specific effects of adenoviral infection. Keywords: ERRalpha, PGC-1alpha, nuclear receptor, orphan nuclear receptor, coactivator, transcription factors
2006-11-10 | GSE5968 | GEO
Project description:Transcriptomic analysis of ERR alpha orphan nuclear receptor
| PRJNA213025 | ENA
Project description:RNA-seq of human and mouse kidneys reveals both known and uncharacterized alternative transcripts derived from genes that are critical for sodium reabsorption and blood pressure regulation.
2020-03-09 | GSE106548 | GEO
Project description:This dataset is part of the manuscript titled "The metabolic regulator ERRalpha, a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cellâs intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer. Primary human mammary epithelial cells were a gift from Dr. J. Marks (Duke University, Durham, NC) and cultured in MEBM (Cambrex, East Rutherford, NJ) with MEGM bullet kit and supplemented with 5mg/ml transferrin and 10-5M isoproterenol. To generate ERR-alpha signature, hMECs were serum starved for 36h followed by infection with MOI=150 of adenoviruses expressing two variants of PGC1alpha, a protein ligand for ERRalpha: PGC-1alpha2x9 or PGC-1alpha L2L3M. PGC-1-2x9 is specific to ERRalpha, while PGC-1-L2L3M lacks the NR box and does not interact with ERRalpha or other nuclear receptors. The generation and purification of variant PGC-1alpha viruses were described previously (Gaillard et al., Molecular Cell 24:5, 2006). Comparable expression levels of the two PGC-1alpha variants were verified by Western immonoblot analysis (data not shown). RNA was collect 16h after infection and purified using RNeasy mini kit (Qiagen, Valencia, CA). Ten independent biological replicates from each virus infection were collected.
2010-11-01 | E-GEOD-23061 | biostudies-arrayexpress
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.
2022-02-16 | GSE165962 | GEO
Project description:Cross-talk between Estrogen Receptor-related Receptor alpha (ERRalpha) and Estrogen Receptor (ERalpha) pathways.
| PRJNA106665 | ENA
Project description:Cardiac metabolic dysfunction is a hallmark of heart failure. Estrogen related receptors ERRalpha and ERRgamma are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential theraputic intervention for heart failure. However, in vivo studies demonstrating the potential utility of ERR agonists for heart failure treatment are lacking, as compounds with pharmackinetics appropriate for in vivo use have not been available. Using a structure-based design approach, we designed and synthesized two structurally distinct pan-ERR agonists, SLU-PP-332 (332) and SLU-PP-915 (915), which significantly improved ejection fraction, ameliorated fibrosis and increased survival associated with pressure overload-induced heart failure without affecting cardiac hypertrophy. Mechanistically, a broad spectrum of metabolic genes was transcriptionally activated by ERR agonists, particulary genes involved in fatty acid metabolism and mitochondrial function. Using both in vitro and in vivo genetic dependency experiments, we show that ERRgamma is the main mediatorof ERR agonism-induced transcriptional regulation and cardioprotection and definitively demonstrated target specificity. Additionally, ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocyte. In summary, ERR agonists maintain oxidative metabolism, which confers cardiac protection against pressure overload-induced heart failure in vivo. Our results provide direct pharmacological evidence supporting the further in vivo development of ERR agonists as novel heart failure theraputics.
2024-01-01 | GSE241075 | GEO
Project description:Cardiac metabolic dysfunction is a hallmark of heart failure. Estrogen related receptors ERRalpha and ERRgamma are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential theraputic intervention for heart failure. However, in vivo studies demonstrating the potential utility of ERR agonists for heart failure treatment are lacking, as compounds with pharmackinetics appropriate for in vivo use have not been available. Using a structure-based design approach, we designed and synthesized two structurally distinct pan-ERR agonists, SLU-PP-332 (332) and SLU-PP-915 (915), which significantly improved ejection fraction, ameliorated fibrosis and increased survival associated with pressure overload-induced heart failure without affecting cardiac hypertrophy. Mechanistically, a broad spectrum of metabolic genes was transcriptionally activated by ERR agonists, particulary genes involved in fatty acid metabolism and mitochondrial function. Using both in vitro and in vivo genetic dependency experiments, we show that ERRgamma is the main mediatorof ERR agonism-induced transcriptional regulation and cardioprotection and definitively demonstrated target specificity. Additionally, ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocyte. In summary, ERR agonists maintain oxidative metabolism, which confers cardiac protection against pressure overload-induced heart failure in vivo. Our results provide direct pharmacological evidence supporting the further in vivo development of ERR agonists as novel heart failure theraputics.
2023-11-21 | GSE239912 | GEO
Project description:PGC-1 transcription factor was customized to limit its interations to ERRalpha. This mutant (2x9) was used to dissect the transcription activation patterns that are attributable to the PGC1-ERR interaction and PGC-1 actions that are independent of ERR. Inactive mutant with the deleted LLXXL motifs (L2L3) and wt PGC-1 were used as negative and positive controls respectively. BGAL-expressing construct was used to control for non-specific effects of adenoviral infection. Experiment Overall Design: Expression constructs for BGAL control and three variants of PGC-1 were introduced into HepG2 cells via adenoviral infection. RNA was isolated 24 hrs post infection and the changes in gene expression were detected using GeneChip technology (Affymetrix). Hybridization was performed on the HG-133 plus 2 platform. The experiment was performed in three biological replicates. Raw expression data were normalized using MAS5.0 algorithm.
2008-06-14 | E-GEOD-5968 | biostudies-arrayexpress