Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 2h in the hypothalamus
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ABSTRACT:
PROVIDER: PRJNA682598 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13198743.fastq.gz | Fastqsanger.gz | |||
| SRR13198744.fastq.gz | Fastqsanger.gz | |||
| SRR13198745.fastq.gz | Fastqsanger.gz | |||
| SRR13198746.fastq.gz | Fastqsanger.gz | |||
| SRR13198747.fastq.gz | Fastqsanger.gz |
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Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162673 | GEO
Project description:Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 6h.
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Project description:Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 24h.
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Project description:Reprogramming of glucocorticoid receptor function by hypoxia: ChIP-seq in the liver.
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Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162155 | GEO
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162100 | GEO
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE163242 | GEO
Project description:Caloric restriction (CR) improves metabolic health. To define how the hepatic glucocorticoid receptor (GR) supports CR-driven metabolic adaptation, we profiled its liver interactome by chromatin immunoprecipitation-mass spectrometry (ChIP-MS). Mouse livers were collected at ZT12 (glucocorticoid peak) under ad libitum or CR feeding. GR immunoprecipitates were compared to IgG controls to identify GR-associated proteins. The dataset reveals diet-dependent GR protein complexes, including transcriptional factors and metabolic coregulators, and serves as a resource for factors linking hormonal and nutritional signals to CR-induced hepatic reprogramming.
2025-11-04 | PXD070287 | Pride
Project description:Background: Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. Methods: To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–tandem mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 4 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Results: Our analysis identified and quantified 2699 lysine acetylation sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant downregulation of proteins that are known to be involved in endocrine hormone secretion. Metabolomic analysis of plasma suggested significant alterations in glycerophospholipid and amino acids metabolism, neuroactive ligand-receptor interaction and serotonergic synapse in children with OSA; these changes may represent potential mechanisms underlying the pathogenesis of OSA in children. Conclusion: This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus, as well as its potential role in endocrine impairment.
2024-10-17 | PXD051767 | Pride
Project description:Here, we investigate the impact of hypoxia on the hepatic response of glucocorticoid receptor (GR) to dexamethasone (DEX) in mice via RNA-sequencing. Hypoxia causes three types of reprogramming of GR: (i) much weaker induction of classical GR response genes by DEX in hypoxia (ii) a number of genes is induced by DEX specifically in hypoxia and (iii) hypoxia induces a group of genes via activation of the hypothalamic-pituitary-adrenal (HPA) axis. Transcriptional profiles are reflected by changed GR-DNA binding as measured by ChIP sequencing. The HPA axis is induced by hypothalamic HIF1α and HIF2α activation and leads to GR-dependent lipolysis and ketogenesis. Acute inflammation, induced by lipopolysaccharide, is prevented by DEX in normoxia but not during hypoxia, and this is attributed to HPA axis activation by hypoxia. We unfold new physiological pathways that have consequences for patients suffering from GC resistance.
| S-SCDT-EMBOR-2021-53083-T | biostudies-other