Orphan Nuclear Receptor ERRγ is required for pancreatic islet beta-cell maturation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56080 | GEO | 2016/04/27
SECONDARY ACCESSION(S): PRJNA242357
REPOSITORIES: GEO
Similar Datasets
Project description:Neurons utilize glucose to generate adenosine triphosphate (ATP) essential for their survival, excitability and synaptic signaling, as well as initiating changes in neuronal structure and function. Defects in oxidative metabolism and mitochondria functions are also associated with aging and diverse human neurological diseases1-4. While neurons are known to adapt their metabolism to meet the increased energy demands of complex behaviors such as learning and memory, the molecular underpinnings regulating this process remain poorly understood4-6. Here we show that the orphan nuclear receptor estrogen related receptor gamma (ERRγ) becomes highly expressed during retinoic-acid induced neurogenesis and is widely expressed in neuronal nuclei throughout the brain. Mechanistically, we show that ERRγ directly orchestrates the expression of networks of genes involved in mitochondrial oxidative phosphorylation and energy generation in neurons. The importance of this regulation is evidenced by decreased adaptive metabolic capacity in cultured neurons lacking ERRγ, and reduced long-term potentiation (LTP) in ERRγ-/- hippocampal slices. Notably, the defect in LTP was rescued by the metabolic intermediate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ exhibit defects in spatial learning and memory. These findings implicate ERRγ in the metabolic adaptations required for long-term memory formation. We used ChIP-Seq analysis to determine the genome-wide binding of ERRγ in neurons derived from ES cells.
2015-09-03 | E-GEOD-47134 | biostudies-arrayexpress
Project description:Neurons utilize glucose to generate adenosine triphosphate (ATP) essential for their survival, excitability and synaptic signaling, as well as initiating changes in neuronal structure and function. Defects in oxidative metabolism and mitochondria functions are also associated with aging and diverse human neurological diseases1-4. While neurons are known to adapt their metabolism to meet the increased energy demands of complex behaviors such as learning and memory, the molecular underpinnings regulating this process remain poorly understood4-6. Here we show that the orphan nuclear receptor estrogen related receptor gamma (ERRγ) becomes highly expressed during retinoic-acid induced neurogenesis and is widely expressed in neuronal nuclei throughout the brain. Mechanistically, we show that ERRγ directly orchestrates the expression of networks of genes involved in mitochondrial oxidative phosphorylation and energy generation in neurons. The importance of this regulation is evidenced by decreased adaptive metabolic capacity in cultured neurons lacking ERRγ, and reduced long-term potentiation (LTP) in ERRγ-/- hippocampal slices. Notably, the defect in LTP was rescued by the metabolic intermediate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ exhibit defects in spatial learning and memory. These findings implicate ERRγ in the metabolic adaptations required for long-term memory formation. We used microarray analysis to compare the genome-wide gene expression changes between wild type (WT) and ERRγ-/- P0 cerebral cortex as it contains mainly neuronal lineage at this stage compared to adult cortex.
2015-09-03 | E-GEOD-47133 | biostudies-arrayexpress
Project description:Neurons utilize glucose to generate adenosine triphosphate (ATP) essential for their survival, excitability and synaptic signaling, as well as initiating changes in neuronal structure and function. Defects in oxidative metabolism and mitochondria functions are also associated with aging and diverse human neurological diseases1-4. While neurons are known to adapt their metabolism to meet the increased energy demands of complex behaviors such as learning and memory, the molecular underpinnings regulating this process remain poorly understood4-6. Here we show that the orphan nuclear receptor estrogen related receptor gamma (ERRγ) becomes highly expressed during retinoic-acid induced neurogenesis and is widely expressed in neuronal nuclei throughout the brain. Mechanistically, we show that ERRγ directly orchestrates the expression of networks of genes involved in mitochondrial oxidative phosphorylation and energy generation in neurons. The importance of this regulation is evidenced by decreased adaptive metabolic capacity in cultured neurons lacking ERRγ, and reduced long-term potentiation (LTP) in ERRγ-/- hippocampal slices. Notably, the defect in LTP was rescued by the metabolic intermediate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ exhibit defects in spatial learning and memory. These findings implicate ERRγ in the metabolic adaptations required for long-term memory formation.
2015-09-03 | GSE47134 | GEO
Project description:Neurons utilize glucose to generate adenosine triphosphate (ATP) essential for their survival, excitability and synaptic signaling, as well as initiating changes in neuronal structure and function. Defects in oxidative metabolism and mitochondria functions are also associated with aging and diverse human neurological diseases1-4. While neurons are known to adapt their metabolism to meet the increased energy demands of complex behaviors such as learning and memory, the molecular underpinnings regulating this process remain poorly understood4-6. Here we show that the orphan nuclear receptor estrogen related receptor gamma (ERRγ) becomes highly expressed during retinoic-acid induced neurogenesis and is widely expressed in neuronal nuclei throughout the brain. Mechanistically, we show that ERRγ directly orchestrates the expression of networks of genes involved in mitochondrial oxidative phosphorylation and energy generation in neurons. The importance of this regulation is evidenced by decreased adaptive metabolic capacity in cultured neurons lacking ERRγ, and reduced long-term potentiation (LTP) in ERRγ-/- hippocampal slices. Notably, the defect in LTP was rescued by the metabolic intermediate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ exhibit defects in spatial learning and memory. These findings implicate ERRγ in the metabolic adaptations required for long-term memory formation.
2015-09-03 | GSE47133 | GEO
Project description:Recent studies have established the importance of ERRγ as a required participant for insulin secretion in pancreatic β cells. Key downstream genes of ERRγ remain unclear in the pancreatic β cell. To understand the molecular role of ERRγ and elucidate potential key candidate genes involved in pancreatic β cells, the eukaryotic expression plasmid containing mouse ERRγ was constructed and transfected into NIT-1 pancreatic β cells. Overexpression of ERRγ was confirmed by Q-RT-PCR and western blot. RNA-seq was conducted to get the gene expression profiling between the experimental cells and control cells. Differentially expressed genes (DEGs) were identified and subsequently analyzed by gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. We found that overexpression of ERRγ in pancreatic β cells enables regulation of the expression of certain genes involved in cell apoptosis and mitochondrial function, such as TFPT, Bcl7c, Dap, Thoc6, Ube2d3, ATP5H, MPV17, and NDUFA6. GO analysis revealed that the DEGs were mainly enriched in biological regulation, cell, and binding. KEGG pathway analysis demonstrated that DEGs were significantly enriched in infectious diseases, translation annd signal transduction. This study helps to further understand and reposition the molecular mechanisms of ERRγ in pancreatic β cells.
2019-11-30 | GSE122805 | GEO
Project description:Genomic analysis of expression in brain, kidney, stomach, liver, and salivary tissues of perinatal ERRγ null and wild type mice.
2009-11-05 | GSE18896 | GEO
Project description: Not available
| S-EPMC8199698 | biostudies-literature
Project description:Here we show that estrogen-related receptor γ (ERRγ) is an essential transcriptional coordinator of both renal mitochondrial and reabsorptive functions. ERRγ is highly and specifically expressed in the RECs, and its expression correlates with kidney function in humans. We generated REC-ERRγ KO mice which developed severe renal mitochondrial and reabsorptive dysfunction and fluid-filled cysts. Transcriptome and cistrome analysis revealed that ERRγ directly regulates mitochondrial metabolism and renal reabsorption. ChIP-reChIP-Seq studies further suggest that ERRγ employs a distinct mechanism to regulate renal reabsorption genes through functional cooperation with hepatic nuclear factor 1 beta (HNF1β), mutations of which cause strikingly similar renal dysfunction and cysts in humans and animals. Together these findings reveal a novel role for ERRγ in simultaneously coordinating a transcriptional program for renal energy production via mitochondria and energy consumption to perform reabsorptive functions required for normal kidney function
2018-04-25 | GSE104905 | GEO
Project description:Here we show that estrogen-related receptor γ (ERRγ) is an essential transcriptional coordinator of both renal mitochondrial and reabsorptive functions. ERRγ is highly and specifically expressed in the RECs, and its expression correlates with kidney function in humans. We generated REC-ERRγ KO mice which developed severe renal mitochondrial and reabsorptive dysfunction and fluid-filled cysts. Transcriptome and cistrome analysis revealed that ERRγ directly regulates mitochondrial metabolism and renal reabsorption. ChIP-reChIP-Seq studies further suggest that ERRγ employs a distinct mechanism to regulate renal reabsorption genes through functional cooperation with hepatic nuclear factor 1 beta (HNF1β), mutations of which cause strikingly similar renal dysfunction and cysts in humans and animals. Together these findings reveal a novel role for ERRγ in simultaneously coordinating a transcriptional program for renal energy production via mitochondria and energy consumption to perform reabsorptive functions required for normal kidney function
2018-04-25 | GSE104906 | GEO
Project description:One-third of all ER+ breast tumors treated with endocrine therapy fail to respond, and the remainder are likely to relapse in the future. Almost all data on endocrine resistance has been obtained in models of invasive ductal carcinoma (IDC). However, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancers diagnosed each year and, while the incidence of IDC has remained relatively constant during the last 20 years, the prevalence of ILC continues to increase among postmenopausal women. We report a new model of Tamoxifen (TAM)-resistant invasive lobular breast carcinoma cells that provides novel insights into the molecular mechanisms of endocrine resistance. SUM44 cells express ER and are sensitive to the growth inhibitory effects of antiestrogens. Selection for resistance to 4-hydroxytamoxifen led to the development of the SUM44/LCCTam cell line, which exhibits decreased expression of estrogen receptor alpha (ERα) and increased expression of the estrogen-related receptor gamma (ERRγ). Knockdown of ERRγ in SUM44/LCCTam cells by siRNA restores TAM sensitivity, and overexpression of ERRγ blocks the growth-inhibitory effects of TAM in SUM44 and MDA-MB-134 VI lobular breast cancer cells. ERRγ-driven transcription is also increased in SUM44/LCCTam, and inhibition of activator protein 1 (AP1) can restore or enhance TAM sensitivity. These data support a role for ERRγ/AP1 signaling in the development of TAM resistance, and suggest that expression of ERRγ may be a marker of poor Tamoxifen response.
2008-11-01 | GSE12708 | GEO