Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 6h.
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ABSTRACT:
PROVIDER: PRJNA680576 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13127004_1.fastq.gz | Fastqsanger.gz | |||
| SRR13127004_2.fastq.gz | Fastqsanger.gz | |||
| SRR13127005_1.fastq.gz | Fastqsanger.gz | |||
| SRR13127005_2.fastq.gz | Fastqsanger.gz | |||
| SRR13127006_1.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 | GSE162100 | GEO
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:Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 2h in the hypothalamus
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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 | GSE163242 | GEO
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-responsive 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-EPMC8728616 | biostudies-literature
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
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:Background Deficient glucocorticoid biosynthesis leading to adrenal insufficiency is life-threatening and is associated with significant co-morbidities. The affected pathways underlying the pathophysiology of co-morbidities due to glucocorticoid deficiency remain poorly understood and require further investigation. Methods To explore the pathophysiological processes related to glucocorticoid deficiency, we have performed global transcriptional, post-transcriptional and metabolic profiling of a cortisol-deficient zebrafish mutant with a disrupted ferredoxin (fdx1b) system. Findings fdx1b−/− mutants show pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b−/− mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients. Interpretation Our study provides a detailed map of metabolic changes induced by glucocorticoid deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency.fdx1b-/- mutants show a pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b-/- mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients. Our study provides a detailed map of metabolic changes induced by glucocorticoid-deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency.
2019-01-21 | GSE107547 | GEO