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Dexamethasone-stimulated DNA methylation of the epigenetic clock CpGs in peripheral blood

ABSTRACT: Whole-genome DNA methylation (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) were analysed to identify glucocorticoid receptor (GR)-mediated changes in DNA methylation. Lifetime stress accelerates epigenetic aging.

ORGANISM(S): Homo sapiens

PROVIDER: GSE74414 | GEO | 2015/11/03

SECONDARY ACCESSION(S): PRJNA300449

REPOSITORIES: GEO

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Dexamethasone-stimulated DNA methylation of the epigenetic clock CpGs in peripheral blood

Project description:Whole-genome DNA methylation (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) were analysed to identify glucocorticoid receptor (GR)-mediated changes in DNA methylation. Lifetime stress accelerates epigenetic aging. DNA methylation was assessed in whole blood at baseline and 3 hours after stimulation with the selective GR agonist dexamethasone (1.5 mg p.o.). Blood was collected in EDTA vacuum tubes prior to extraction. DNA methylation was interrogated for each sample using the HumanMethylation450 BeadChip (Illumina). Supplementary files 'GSE74414_unmethylated_signals_353_CpG.txt', 'GSE74414_methylated_signals_353_CpG.txt', and 'GSE74414_detection.p.values_353_CpG.txt' include the raw data for the 353 CpGs used in the analysis in the associated manuscript. Supplementary file 'GSE74414_beta_values_353_CpG.txt' includes the processed data for the 353 CpGs used in the analysis in the associated manuscript. The raw and processed data for the remaining features included in Platform GPL13534 are embargoed.

2015-11-03 | E-GEOD-74414 | biostudies-arrayexpress

Dexamethasone stimulated gene expression in peripheral blood

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Dexamethasone stimulated gene expression in peripheral blood

Project description:Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) were analysed to identify glucocorticoid receptor (GR)-mediated changes in gene expression. A Dexamethasone Suppression Test was performed in 297 subjects. Baseline and stimulated (3 hours after 1.5 mg dexamethasone p.o.) whole blood samples were analyzed using Illumina Human HT-12 v3 and v4 arrays.

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Project description:The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. We identified glucocorticoid receptor (GR) activity as modulator of enzalutamite sensitivity in the VCaP prostate cancer cell line. The GR agonist dexamethasone was sufficient to confer enzalutamide resistance whereas a GR antagonist restored sensitivity. These expression profiling data demonstrate that GR transcriptional activity overlaps with that of AR in the VCAP model.

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Project description:The glucocorticoid receptor (GR) is a transcription factor that localizes to the nucleus and reuglates gene expression upon binding of a glucocorticoid ligand such as dexamethasone. We perform nascent transcriptional profiling of C7 ALL cells following treatment with dexamethasone to evaluate the immediate transcriptional effects of GR. We find 51 dynamic genes (46 activated, 5 repressed) after 1 hour treatment and 141 dynamic genes (70 activated and 71 repressed) after 4 hour treatment. We input RNA polymerase density in pause and gene body regions into a mathematical model designed to quantify rate changes of individual transcriptional steps. We find that dexamethasone treatment primarily activates genes by inducing pause release rate.

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