A Characterization of the Chromatin Landscape and the Glucocorticoid Receptor Cistrome in Mouse Cerebral Cortical Embryonic Neural Stem and Progenitor Cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE175850 | GEO | 2022/05/25
REPOSITORIES: GEO
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Project description:An unresolved molecular paradox is how the glucocorticoid receptor (GR) activates some genes while potently repressing others. We carried out genome-wide localization and expression profiling experiments in primary bone marrow-derived mouse macrophages treated with Dexamethasone in the presence or absence of LPS. Unexpectedly, we find that the anti-inflammatory GR cistrome, which is principally composed of 'canonical' GREs colocalizing with NFkB and AP-1 co-enriched with the myeloid lineage factors C/EBP and Pu.1, is shaped by TLR4-directed chromatin dynamics, suggesting that context rather than sequence may be a critical determinant of function. Identification of GR, cJun, NFkB(p65) binding sites in primary bone-marrow derived macrophages unstimulated and LPS-stimulated (3hrs) that were untreated or pre-treated with Dexamethasone for 16 hrs
2012-12-04 | E-GEOD-31796 | biostudies-arrayexpress
Project description:In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth. Total RNA isolated from isogenic HEK293 cell lines stably expressing either wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR) treated with either vehicle (EtOH) or 100 nM of dexamethasone (dex) for 6h. All conditions are performed in triplicate
2013-11-05 | E-GEOD-48328 | biostudies-arrayexpress
Project description:In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth. Total RNA isolated from U2Os cell lines stably expressing either wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR) treated with either vehicle (EtOH) or 100 nM of dexamethasone (dex) for 6h.
2013-11-05 | E-GEOD-48330 | biostudies-arrayexpress
Project description:Here we have analyzed the role of interferon regulatory factor-2 binding protein-2 (IRF2BP2) in glucocorticoid and tumor necrosis factor alpha (TNF) signaling. We used ChIP-seq to analyze chromatin binding of IRF2BP2 in glucocorticoid (dexamethasone, dex) and vehicle treated HEK293 cells expressing GR (HEK293-GR). Furthermore, we used RNA-seq to analyze how silencing of IRF2BP2 modulates transcriptional responses to dex treatment in HEK293-GR cells, and dex, TNF and co-treatment (dex and TNF, DT) in A549 cells.
2019-06-03 | GSE124636 | GEO
Project description:We performed RNA sequencing in Mouse Embryonic Fibroblasts (MEFs) of GR wild-type and GR Zn. Cells were treated with: vehicle (EtOH), Dexamethasone (Dex), Lipopolysaccharide (LPS) or Dex+LPS. We show that GR Zn does not regulate any GR target gene
2019-12-31 | GSE124919 | GEO
Project description:To investigate the role of HES1 during glucocorticoid signaling in bone sarcoma cells (U2OS-GR cells) , we employed whole-genome microarray expressions in mRNA extracted from control U2OS-GR and Hes1-overexpressed U2OS-GR cells. RNA isolated from control U2OS-GR and Hes1-overexpressed U2OS-GR cells treated with VEH or Dexamethasone.
2014-01-21 | E-GEOD-52727 | biostudies-arrayexpress
Project description:An unresolved molecular paradox is how the glucocorticoid receptor (GR) activates some genes while potently repressing others. We carried out genome-wide localization and expression profiling experiments in primary bone marrow-derived mouse macrophages treated with Dexamethasone in the presence or absence of LPS. Unexpectedly, we find that the anti-inflammatory GR cistrome, which is principally composed of ‘canonical’ GREs colocalizing with NF-κB and AP-1 co-enriched with the myeloid lineage factors C/EBP and Pu.1, is shaped by TLR4-directed chromatin dynamics, suggesting that context rather than sequence may be a critical determinant of function.
2012-11-01 | GSE31793 | GEO
Project description:An unresolved molecular paradox is how the glucocorticoid receptor (GR) activates some genes while potently repressing others. We carried out genome-wide localization and expression profiling experiments in primary bone marrow-derived mouse macrophages treated with Dexamethasone in the presence or absence of LPS. Unexpectedly, we find that the anti-inflammatory GR cistrome, which is principally composed of 'canonical' GREs colocalizing with NFkB and AP-1 co-enriched with the myeloid lineage factors C/EBP and Pu.1, is shaped by TLR4-directed chromatin dynamics, suggesting that context rather than sequence may be a critical determinant of function.
2012-12-04 | GSE31796 | GEO
Project description:The glucocorticoid and progesterone receptors (GR and PR) are closely related members of the steroid receptor family. Despite sharing similar structural and functional characteristics; the cognate hormones display very distinct physiological responses. In mammary epithelial cells, PR activation is associated with the incidence and progression of breast cancer, whereas the GR is related to growth suppression and differentiation. Despite their pharmacological relevance, only a few studies have compared GR and PR activities in the same system. Using a PR+/GR+ breast cancer cell line, here we report that either glucocorticoid-free or dexamethasone-activated GR inhibits progestin-dependent gene expression associated to epithelial-mesenchymal-transition and cell proliferation. When both receptors are activated with their cognate hormones, PR and GR can form part of the same complex according to co-immunoprecipitation, quantitative microscopy, and sequential ChIP experiments. Moreover, genome-wide studies in cells treated with either dexamethasone or R5020, revealed the presence of several regions co-bound by both receptors. Surprisingly, GR also binds novel genomic sites in cells treated with R5020 alone. This progestin-induced GR binding was enriched in REL DNA motifs and located close to genes coding for chromatin remodelers. Understanding GR behavior in the context of progestin-dependent breast cancer could provide new targets for tumor therapy.
2019-11-25 | GSE126859 | GEO
Project description:In addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
2013-11-05 | GSE48328 | GEO