Cistromic reprogramming of the diurnal glucocorticoid hormone response by high fat diet
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ABSTRACT:
PROVIDER: PRJNA428302 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10182179.fastq.gz | Fastqsanger.gz | |||
| SRR10182179_1.fastq.gz | Fastqsanger.gz | |||
| SRR10182179_2.fastq.gz | Fastqsanger.gz | |||
| SRR10182180.fastq.gz | Fastqsanger.gz | |||
| SRR10182180_1.fastq.gz | Fastqsanger.gz |
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Project description:The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2019-10-21 | GSE108690 | GEO
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Project description:We performed ChIP-seq targeting the glucocorticoid receptor (GR) in the U2OS-GR cell line. The cell line is derived from U2OS ATTC:HTB-96 and stably transfected with an expression construct for rat GR. The cells were treated with 100 nM dexamethasone for 4 hours, washed 2x with PBS and cultured in hormone-free medium for 24 hours before harvest.
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Project description:There is growing evidence that energy metabolism and insulin action are regulated by mechanisms that follow a diurnal rhythm and it has been proposed that defects in Akt signalling are associated with the pathophysiology of metabolic disease. It is therefore important to investigate these parameters under physiology of the free-living state. We therefore examined the insulin action in muscle of chow or high fat, high sucrose diet-fed (HFHS) rats during the normal diurnal cycle. HFHS animals displayed hyperinsulinemia, however had reduced systemic glucose disposal and impaired muscle glucose uptake during the feeding period. Proteomics and phosphoproteomics was performed over the diurnal cycle in chow and HFHS rats.
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Project description:Steroid hormone receptors such as the Glucocorticoid Receptor (GR) mediate the transcriptional response to hormones and are frequently targeted in the treatment of human diseases. Experiments using bulk populations of cells have provided a detailed picture of the global transcriptional hormone response but are unable to interrogate cell-to-cell transcriptional heterogeneity. To examine the glucocorticoid response in individual cells, we performed single cell RNA sequencing (scRNAseq). The transcriptional response to hormone was robustly detected in individual cells and scRNAseq provided additional statistical power to identify over 100 GR-regulated genes that were not detected in bulk RNAseq. scRNAseq also revealed a large degree of cell-to-cell variability in the hormone response. On average, individual hormone-treated cells showed a response at only 30% of the total set of GR target genes. Understanding the basis of this heterogeneity will be critical for the development of more precise models of steroid hormone signaling.
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Project description:Glucocorticoid receptor profiling (ChIP-seq) in U2OS-GR cells 24 hours after hormone washout
| PRJEB41992 | ENA