Candidate genes mediated by estrogen-related receptor gamma (ERRγ) in pancreatic β cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA506420 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8234790_1.fastq.gz | Fastqsanger.gz | |||
| SRR8234790_2.fastq.gz | Fastqsanger.gz | |||
| SRR8234791_1.fastq.gz | Fastqsanger.gz | |||
| SRR8234791_2.fastq.gz | Fastqsanger.gz | |||
| SRR8234792_1.fastq.gz | Fastqsanger.gz |
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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:Estrogen-related receptor γ (ERRγ) serves a critical O2-dependent regulatory role in differentiation of human cytotrophoblasts to syncytiotrophoblast. In this study, we investigated expression of genes encoding tissue kallikreins (KLK1) and voltage-gated K+ channels (KV7) during differentiation of human trophoblasts in culture and the roles of ERRγ and O2 tension in their regulation. Expression of KLK1 and the KV7 channel subunits, KCNQ1, KCNE1, KCNE3, KCNE5, increased during differentiation of cultured human trophoblast cells in a 20% O2 environment. Notably, together with ERRγ, expression of KLK1, KCNQ1, KCNE1, KCNE3 and KCNE5 was markedly reduced when cells were cultured in a hypoxic environment (2% O2). Moreover, upon transduction of trophoblast cells with shRNAs for endogenous ERRγ, KLK1, KCNQ1, KCNE1 and KCNE3 expression was significantly decreased. Promoter and site-directed mutagenesis studies in transfected cells identified putative ERRγ response elements (ERREs) within the KLK1 and KCNE1 5'-flanking regions required for ERRγ -stimulated transcriptional activity. Binding of endogenous ERRγ to these ERREs increased during trophoblast differentiation in culture and was inhibited by hypoxia. The KV7 blocker linopirdine reduced hCG secretion and aggregation of cultured human trophoblasts, suggesting a possible role of KV7 channels in cell fusion and differentiation. Illumina gene expression arrays of cultured human trophoblast cells revealed several genes upregulated during syncytiotrophoblast differentiation and downregulated upon ERRγ knockdown involved in cell differentiation, adhesion, and synthesis of steroid and peptide hormones required for placental development and function. Collectively, these findings suggest that ERRγ mediates O2-dependent expression of genes involved in human trophoblast differentiation, function and vascular homeostasis.
2013-04-30 | GSE46463 | GEO
Project description:Androgens are central to prostate cancer (PCa) development and targeting this pathway is currently the main therapeutic axis in the clinic, but the mechanism by which androgen signaling contributes to the oncometabolic state of PCa cells remains to be fully elucidated. The intersection of gene expression, binding-events and motif finding analyses following androgen exposure identified a metabolic gene signature associated with the action of estrogen-related receptors (ERRs). Unexpectedly, we show that ERRγ acts as a negative regulator of mitochondrial respiration in the context of PCa, and that AR-dependent direct repression of ERRγ promotes the reactivation of a functional TCA cycle. This metabolic state, which parallels the loss of ERRγ expression, was observed in both androgen-dependent and castration-resistant PCa and was associated with cell proliferation. Interrogation of several clinical studies revealed a strong inverse relationship between ERRγ expression and the severity of the disease. Our study uncovers a novel mechanism by which AR-dependent repression of ERRγ contributes to the reprogramming of PCa cell metabolism to favor mitochondrial activity and cell proliferation. We used microarrays to investigate the transcriptional regulation of metabolic genes by 72h treatment with R1881, a synthetic androgens, with or without repression of the estrogen-related receptor gamma, in LNCaP prostate cancer cells.
2016-12-06 | GSE86781 | 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. 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: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: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: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
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