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RNAseq measurement of cortisol induced gene expression change under knockout of glucocorticoid receptor (nr3c1)

ABSTRACT: RNAseq measurement of cortisol induced gene expression change under knockout of glucocorticoid receptor (nr3c1)

PROVIDER: PRJNA605204 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11039783_1.fastq.gz	Fastqsanger.gz
	SRR11039783_2.fastq.gz	Fastqsanger.gz
	SRR11039784_1.fastq.gz	Fastqsanger.gz
	SRR11039784_2.fastq.gz	Fastqsanger.gz
	SRR11039785_1.fastq.gz	Fastqsanger.gz

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RNAseq measurement of cortisol induced gene expression change under knockout of glucocorticoid receptor (nr3c1)

Project description:We found that GR mediates most of the effects of the treatment, and paradoxically, that the transcriptome of cortisol-treated larvae is more like that of larvae lacking a GR than that of larvae with a GR, suggesting that the cortisol-treated larvae develop GR resistance.

2020-07-15 | GSE144884 | GEO

RNAseq measurement of cortisol induced gene expression change under knockout of Klf9

Project description:RNAseq measurement of cortisol induced gene expression change under knockout of Klf9

| PRJNA605203 | ENA

RNAseq measurement of cortisol induced gene expression change under knockout of Klf9

Project description:We found that a frameshift deletion introduced into exon 1 of zebrafish klf9 eliminates the DNA binding domain and significantly reduces expression of the mature transcript. RNA-seq shows that klf9 is required for the pro-inflammatory transcriptomic effects of chronic cortisol treatment. klf9 is one of a core set of genes consistently found to be upregulated by chronic cortisol exposure.

2020-07-15 | GSE144885 | GEO

Thalidomide in Total Therapy 2 Overcomes Inferior Prognosis of Myeloma with Low Expression of the Glucocorticoid Receptor Gene NR3C1

Project description:Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the correlation of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 with other clinical features. Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)–derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to Total Therapy 2 (TT2). The effect of the expression of NR3C1 at baseline (previously published under GSE2685) and at relapse was analyzed in the context of treatment (thalidomide vs. no thalidomide) and other clinical parameters.

2012-11-05 | E-GEOD-38627 | biostudies-arrayexpress

The auophagy receptor SQSTM1/p62 mediates anti-inflammatory actions of the selective NR3C1/glucocorticoid receptor modulator compound A (CpdA) in macrophages

Project description:Glucocorticoids are widely used to treat inflammatory disorders; however, prolonged use of glucocorticoids results in side effects including osteoporosis, diabetes and obesity. Compound A (CpdA), identified as a selective NR3C1/glucocorticoid receptor (nuclear receptor subfamily 3, group C, member 1) modulator, exhibits an inflammation-suppressive effect, largely in the absence of detrimental side effects. To understand the mechanistic differences between the classic glucocorticoid dexamethasone (DEX) and CpdA, we looked for proteins oppositely regulated in bone marrow-derived macrophages using an unbiased proteomics approach. We found that the autophagy receptor SQSTM1 but not NR3C1 mediates the anti-inflammatory action of CpdA. CpdA drives SQSTM1 upregulation by recruiting the NFE2L2 transcription factor to its promoter. In contrast, the classic NR3C1 ligand dexamethasone recruits NR3C1 to the Sqstm1 promoter and other NFE2L2-controlled gene promoters, resulting in gene downregulation. Both DEX and CpdA induce autophagy, with marked different autophagy characteristics and morphology. Suppression of LPS-induced Il6 and Ccl2 genes by CpdA in macrophages is hampered upon Sqstm1 silencing, confirming that SQSTM1 is essential for the anti-inflammatory capacity of CpdA, at least in this cell type. Together, these results demonstrate how off-target mechanisms of selective NR3C1 ligands may contribute to a more efficient anti-inflammatory therapy.

2019-06-11 | PXD012121 | Pride

Real-time quantitative PCR analysis of cortisol-indeced sex change in epinephelus coioides

Project description:Cortisol was injected into the protogynous epinephelus coioides to investigate the role of this hormone on sex change. Following injection, we evaluated sex-related gene expression during the processes of cortisol-induced sex change in epinephelus coioides.

2020-01-02 | GSE142814 | GEO

Harsh Parenting Predicts Novel HPA Receptor Gene Methylation and NR3C1 Methylation Predicts Cortisol Daily Slope in Middle Childhood

Project description:Adverse experiences in childhood are associated with altered hypothalamic pituitary adrenal axis function and negative health outcomes throughout life. It is now commonly accepted that abuse and neglect can alter epigenetic regulation of HPA genes. Accumulated evidence suggests harsh parenting practices such as spanking are also strong predictors of negative health outcomes. We predicted harsh parenting at 2.5 years old would predict HPA gene DNA methylation similarly to abuse and neglect, and cortisol output at 8.5 years old. Saliva samples were collected three times a day across three days to estimate cortisol diurnal slopes. Methylation was quantified using the Illumina Infinium MethylationEPIC array BeadChip (850K) with DNA collected from buccal cells. We used principal components analysis to compute a summary statistic for CpG sites across candidate genes. The first and second components were used as outcome variables in mixed linear regression analyses with harsh parenting as a predictor variable. We found harsh parenting significantly predicted methylation of several HPA axis genes, including novel gene associations with AVPRB1, CRHR1, CRHR2, and MC2R (FDR corrected p < 0.05). Further, we found NR3C1 methylation predicted a steeper diurnal cortisol slope. Our results extend the current literature by demonstrating harsh parenting may influence DNA methylation similarly to more extreme early life experiences such as abuse and neglect. Further, we show NR3C1 methylation is associated with diurnal HPA function. Elucidating the molecular consequences of harsh parenting on health can inform best parenting practices and provide potential treatment targets for common complex disorders.

2021-04-01 | GSE147058 | GEO

Cleavage Under Targets and Release Using Nuclease (CUT&RUN) assay of glucocorticoid receptor (NR3C1) in aggressive B-cell lymphomas [JC3]

Project description:We determined that glucocorticoid treatment (prednisolone) affects oncogenic signaling in aggressive B-cell lymphomas. We sought to identify genes directly controlled and bound by NR3C1.

2023-03-17 | GSE226873 | GEO

Thalidomide in Total Therapy 2 Overcomes Inferior Prognosis of Myeloma with Low Expression of the Glucocorticoid Receptor Gene NR3C1

2012-11-05 | GSE38627 | GEO

The knockdown of maternal glucocorticoid receptor mRNA alters embryo development in zebrafish

Project description:In zebrafish, ovulated oocytes contain both cortisol deposited from the maternal circulation and maternal mRNA for the glucocorticoid receptor (gr mRNA), which is spread as granular structures throughout the central ooplasm. At the 1-cell stage (0.2 hpf), this transcript is relocated by streamers in the blastodisc area and equally partitioned among blastomeres. At 15 hpf, it is replaced by the zygotic transcript. Morpholino knockdown was applied to block translation (grATG1MO or MO2-nr3c1 and grATG2MO or MO3-nr3c1) of both maternal and zygotic gr transcripts, while a missplicing morpholino (grmismMO or MO4-nr3c1) was used to block post-transcriptionally the zygotic transcript alone. MO2-nr3c1 and MO3-nr3c1 (but not MO4-nr3c1) treatment produced craniofacial and caudal malformations in 1-dpf embryos and 5-dpf larvae, which were also affected by pericardial oedema, persistent yolk sac, reduced subintestinal veins, altered neurogenesis and uninflated swim bladder. Such effects were rescued with trout gr2 mRNA. Pangenomic microarray analysis revealed that 114 and 37 highly expressed transcripts were up- and down-regulated, respectively, by maternal GR protein deficiency in 5-hpf embryos. Similar alterations were found at 10 hpf. These effects were confirmed by real-time PCR of 2 up- (casp8, grp1 and igf2a) and 1 down-regulated transcripts (mcm6) evaluated at 4, 8 and 12 hpf. As the contents of transcripts were modified already at 4 hpf, it seems that the lack of GR affects both ways the molecular machinery for the degradation of maternal mRNAs. These results indicate that the maternal gr transcript participates in the maternal programming of zebrafish development. MO2-nr3c1 morphants were compared with MO2-nr3c1-5m morphants at 5 hpf and 10 hpf. MO2-nr3c1 morphants were compared with wild type (WT) at 5 hpf and 10 hpf. MO2-nr3c1 is a morpholino selected to knockdown translation of gr mRNA. MO2-nr3c1-5m is a specific control morpholino.

2011-11-16 | E-GEOD-25517 | biostudies-arrayexpress

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