Similar Datasets
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:ERRγ coordinates a transcriptional program of mitochondrial and renal reabsorptive functions implicated in kidney disease
| PRJNA414114 | ENA
Project description:ERRγ coordinates a transcriptional program of mitochondrial and renal reabsorptive functions implicated in kidney disease [RNA-seq]
| PRJNA414151 | ENA
Project description:ERRγ coordinates a transcriptional program of mitochondrial and renal reabsorptive functions implicated in kidney disease [ChIP-seq]
| PRJNA414152 | ENA
Project description:Orphan nuclear receptor ERRγ is a member of nuclear receptor superfamily that regulates several important cellular processes including hepatic glucose and alcohol metabolism. However, mechanistic understanding of transcriptional regulation of the ERRγ gene remains to be elucidated. Here, we report that activating transcription factor 6α (ATF6α), an endoplasmic reticulum (ER)-membrane-bound basic leucine zipper (bZip) transcription factor, directly regulates ERRγ gene expression in response to ER stress. ATF6α binds to ATF6α responsive element in the ERRγ promoter. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) is required for this transactivation. Chromatin immunoprecipitation (ChIP) assay confirmed the binding of both ATF6α and PGC1α on the ERRγ promoter. ChIP assay demonstrated histone H3 and H4 acetylation occurs at the ATF6α and PGC1α binding site. Of interest, ERRγ along with PGC1α induce ATF6α gene transcription upon ER stress. ERRγ binds to an ERRγ responsive element in the ATF6α promoter. ChIP assay confirmed that both ERRγ and PGC1α bind to a site in the ATF6α promoter that exhibits histone H3 and H4 acetylation. Overall, for the first time our data show a novel pathway of cross talk between nuclear receptors and ER-membrane-bound transcription factors and suggest a positive feed-forward loop regulates ERRγ and ATF6α gene transcription.
| S-EPMC3737538 | biostudies-literature
Project description:Diabetic kidney disease (DKD) is one of the common chronic microvascular complications of diabetes in which mitochondrial disorder plays an important role in its pathogenesis. The current study delved into the single-cell level transcriptome heterogeneity of mitochondrial homeostasis in db/db mice, an animal model for study of type 2 diabetes and DKD, with single-cell RNA sequencing (scRNA-Seq) and bulk RNA-seq analyses. From the comprehensive dataset comprising 13 meticulously captured and authenticated renal cell types, an unsupervised cluster analysis of mitochondria-related genes within the descending loop of Henle, collecting duct principal cell, endothelial, B cells and macrophage, showed that they had two types of cell subsets, i.e., health-dominant and DKD-dominant clusters. Pseudotime analysis, cell communication and transcription factors forecast resulted in identification of the hub differentially expressed genes between these two clusters and unveiled that the hierarchical regulatory network of receptor-TF-target genes was triggered by mitochondrial degeneration. Furthermore, the collecting duct principal cells were found to be regulated by the decline of Fzd7, which contributed to the impaired cellular proliferation and development, apoptosis and inactive cell cycle, as well as diminished capacity for material transport. Thereby, both scRNA-Seq and bulk RNA-Seq data from the current study elucidate the heterogeneity of mitochondrial disorders among distinct cell types, particularly in the collecting duct principal cells and B cells during the DKD progression and drug administration, which provide novel insights for better understanding the pathogenesis of DKD.
| S-EPMC10487965 | biostudies-literature
Project description:The differentiated functions of the human airway epithelium are coordinated by a complex network of transcription factors. These include the pioneer factors Forkhead box A1 and A2 (FOXA1 and FOXA2), which are well studied in several tissues, but their role in airway epithelial cells is poorly characterized. Here, we define the cistrome of FOXA1 and FOXA2 in primary human bronchial epithelial (HBE) cells by chromatin immunoprecipitation with deep-sequencing (ChIP-seq). Next, siRNA-mediated depletion of each factor is used to investigate their transcriptome by RNA-seq. We found that, as predicted from their DNA-binding motifs, genome-wide occupancy of the two factors showed substantial overlap; however, their global impact on gene expression differed. FOXA1 is an abundant transcript in HBE cells, while FOXA2 is expressed at low levels, and both these factors likely exhibit autoregulation and cross-regulation. FOXA1 regulated loci are involved in cell adhesion and the maintenance of epithelial cell identity, particularly through repression of genes associated with epithelial to mesenchymal transition (EMT). FOXA1 also directly targets other transcription factors with a known role in the airway epithelium such as SAM-pointed domain-containing Ets-like factor (SPDEF). The intersection of the cistrome and transcriptome for FOXA1 revealed enrichment of genes involved in epithelial development and tissue morphogenesis. Moreover, depletion of FOXA1 was shown to reduce the transepithelial resistance of HBE cells, confirming the role of this factor in maintaining epithelial barrier integrity.
| S-EPMC7468843 | biostudies-literature
Project description:Neurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate energy essential for survival, function, and behavioral output. Unlike most cells that burn both fat and sugar, neurons only burn sugar. Despite its importance, how neurons meet the increased energy demands of complex behaviors such as learning and memory is poorly understood. Here we show that the estrogen-related receptor gamma (ERRγ) orchestrates the expression of a distinct neural gene network promoting mitochondrial oxidative metabolism that reflects the extraordinary neuronal dependence on glucose. ERRγ(-/-) neurons exhibit decreased metabolic capacity. Impairment of long-term potentiation (LTP) in ERRγ(-/-) hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ in cerebral cortex and hippocampus exhibit defects in spatial learning and memory. These findings implicate neuronal ERRγ in the metabolic adaptations required for memory formation.
| S-EPMC4393848 | biostudies-literature
Project description:Reactive oxygen species (ROS)-dependent signaling pathways from chloroplasts and mitochondria merge at the nuclear protein RADICAL-INDUCED CELL DEATH1 (RCD1). RCD1 interacts in vivo and suppresses the activity of the transcription factors ANAC013 and ANAC017, which mediate a ROS-related retrograde signal originating from mitochondrial complex III. Inactivation of RCD1 leads to increased expression of mitochondrial dysfunction stimulon (MDS) genes regulated by ANAC013 and ANAC017. Accumulating MDS gene products, including alternative oxidases (AOXs), affect redox status of the chloroplasts, leading to changes in chloroplast ROS processing and increased protection of photosynthetic apparatus. ROS alter the abundance, thiol redox state and oligomerization of the RCD1 protein in vivo, providing feedback control on its function. RCD1-dependent regulation is linked to chloroplast signaling by 3'-phosphoadenosine 5'-phosphate (PAP). Thus, RCD1 integrates organellar signaling from chloroplasts and mitochondria to establish transcriptional control over the metabolic processes in both organelles.
| S-EPMC6414205 | biostudies-literature