Gene expression profiles of U2OS human osteosarcoma cell lines with ablation of NR1D1 or NR1D2 gene
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE248721 | GEO | 2024/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:Nuclear receptor subfamily 1 group D member 1 (NR1D1), also known as Rev-Erbα, is a circadian clock component that functions as a transcriptional repressor which coordinates circadian rhythm and cell metabolism. Altered circadian clock characteristics have been shown in malignant thyroid neoplasms, and NR1D1 is one of the recurrence-associated genes in papillary thyroid cancer. We aimed to investigate the biological role of NR1D1 in thyroid cancer cells.
2024-02-22 | GSE255015 | GEO
Project description:Heme is the endogenous ligand for the constitutively repressive REV-ERB nuclear receptors, REV-ERBα (NR1D1) and REV-ERBβ (NR1D2), but how heme regulates REV-ERB activity remains unclear. While cellular studies indicate heme is required for the REV-ERBs to bind the corepressor NCoR and repress transcription, fluorescence-based biochemical assays and crystal structures suggest that heme displaces NCoR. Here, we found that heme artifactually influences detection of NCoR interaction in fluorescence-based assays. Using fluorescence-independent methods, including isothermal titration calorimetry, NMR spectroscopy, and XL-MS, we determined that heme remodels the thermodynamic profile of NCoR binding to REV-ERBβ ligand-binding domain (LBD) and directly increases LBD binding affinity for an NCoR interaction motif. We further report two crystal structures of REV-ERBβ LBD cobound to heme and NCoR peptides, which reveal the heme-dependent NCoR binding mode. By resolving previous contradictory biochemical, structural, and cellular studies, our findings should facilitate renewed progress toward understanding heme-dependent REV-ERB activity.
2021-02-24 | PXD021761 | Pride
Project description:Alzheimer’s disease is associated with disrupted circadian rhythms and clock gene expression. REV-ERBα (Nr1d1) is a circadian transcriptional repressor involved in the regulation of lipid metabolism and macrophage function. While global REV-ERBα deletion increases microglial activation and mitigates amyloid plaque formation, the cell-autonomous effects of microglial REV-ERBα deletion in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deficient enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male microglia. Inflammation and LD accumulation combine to inhibit microglial tau phagocytosis, which can be partially rescued by blockage of lipid droplet formation. Microglial REV-ERBα deletion exacerbates tau aggregation and neuroinflammation in P301S and AAV-P301L tauopathy models in male, but not female mice. These data demonstrate the importance of microglial lipid droplets in tau accumulation and reveal REV-ERBα as a therapeutically accessible, sex-dependent regulator of microglial inflammatory signaling, lipid metabolism, and tauopathy.
2023-08-09 | PXD043877 | Pride
Project description:Alzheimer’s disease is associated with disrupted circadian rhythms and clock gene expression. REV-ERBα (Nr1d1) is a circadian transcriptional repressor involved in the regulation of lipid metabolism and macrophage function. While global REV-ERBα deletion increases microglial activation and mitigates amyloid plaque formation, the cell-autonomous effects of microglial REV-ERBα on tau pathology are unexplored. Here, we show that microglial REV-ERBα deletion enhances inflammatory signaling, disrupts lipid metabolic processes, and causes lipid droplet (LD) accumulation specifically in male microglia. Inflammation and LD accumulation combine to inhibit microglial tau phagocytosis, which can be partially rescued by blockage of lipid droplet formation. Microglial REV-ERBα deletion exacerbates tau aggregation and neuroinflammation in P301S and AAV-P301L tauopathy models in male, but not female mice. These data demonstrate the importance of microglial lipid droplets in tau accumulation and reveal REV-ERBα as a therapeutically accessible, sex-dependent regulator of microglial inflammatory signaling, lipid metabolism, and tauopathy.
2023-07-12 | GSE236875 | GEO
Project description:The nuclear receptors (NRs) REV-ERBα and β, encoded by Nr1d1 and Nr1d2, link circadian rhythms and metabolism. REV-ERB lacks the canonical NR activation domain, and thus functions as a transcriptional repressor. Like other NRs, REV-ERBs can be regulated by ligands, including naturally occurring heme, which potentiate their repressive activity. Attempts to pharmacologically target REV-ERBs by the use of putatively specific synthetic agonists, particularly SR90096, have suggested a wide range of beneficial effects in healthy as well as diseased animal models and cell systems. For instance, Sulli et al. recently reported that REV-ERB activation by SR9009 is specifically lethal to cancer (stem) cells but not other cell types. Because REV-ERBs are core components of the molecular clock, the results were interpreted as a link between the body’s circadian timekeeping system and cancer. Moreover, increased energy expenditure after SR9009 administration decreases obesity in mice, and the reported activity of SR9009 as an exercise mimetic in skeletal muscle have resulted in online sales of the compound as a performance-enhancing drug, with advertisements reassuringly highlighting REV-ERBs as the molecular target (https://www.evolutionary.org/stenabolic-sr9009-review; https://www.simplyanabolics.com/sarms/sr9009-stenabolic/).
2019-05-08 | GSE123312 | GEO
Project description:We report here that REV-ERBα influences nuclear localization of the glucocorticoid receptor and vice versa. As a consequence these two nuclear receptors influence each others transcriptome. REV-ERBα (Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, Nr3c1) influences similar processes, but is not part of the circadian clock mechanism although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes we studied the interplay between these two nuclear receptors. We found that REV-ERBα competes with GR for binding to HSP90, a chaperone responsible for the activation of substrate proteins to ensure survival of a cell. This competition affected stability and nuclear localization of GR, thereby affecting GR target gene expression such as IκB and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence each others transcritpional potential indicating that the transcriptional landscape is strongly dependent on dynamic processes at the protein level.
2016-10-01 | GSE79087 | GEO
Project description:Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev-erb alpha) has been linked to circadian rhythm regulation, mood-related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward-related genes to modulate social reward. In this study, we applied our insights from the maternal state to non-parental adult mice to determine whether decreases in Nr1d1 expression in NAc via adeno-associated viral (AAV) vectors and short hairpin RNA (shRNA)-mediated gene knockdown were sufficient to modulate social reward and mood-related behaviors. We also used microarray analysis of to identify gene expression alterations induced by the lowering of Nr1d1 expression. We used microarrays to evalute the effects of knockdown of mRNA for Nr1d1 in nuclues accumbens on gene expression.
2018-09-01 | GSE110363 | GEO
Project description:Rev-erbα/β are druggable components of the molecular circadian clock. Rev-erb agonists can mitigate pressure overload-induced cardiac hypertrophy and myocardial infarction in mice, while Rev-erb antagonist increases myocardial ischemia-reperfusion tolerance ex vivo at the sleep-to-wake transitionHow cardiac Rev-erb regulates heart function has not been studied in vivo. ChIP-seq of Rev-erbα in the heart confirmed the robust diurnal rhythmicity of Rev-erbα genome binding with about 5 times more binding at ZT9 than at ZT21.
2021-12-08 | GSE153150 | GEO
Project description:Deletion of the circadian clock proteins Bmal1 or Nr1d1 (also known as Rev-Erb-alpha) can not only cause circadian dysfunction, but also neuroinflammation in the hippocampus. In this array, 3 wt, 2 Bmal1 KO, and 2 Nr1d1 KO mice, all 5mo, were kept in standard 12h:12h light:dark condition, then anesthetized and perfused with PBS+heparin. Mice were harvest in between noon and 3pm. Whole hippocampus was removed and flash frozen, then RNA was extracted using Trizol reagent and PureLink RNA columns, per manufacturers instructions. RNA microarray analysis was performed by the Washington Univ. Genome Technology Access Center using Agilent Mouse 4x44K mouse V2 array.
2019-02-11 | E-MTAB-7590 | biostudies-arrayexpress
Project description:To investigate the role of NR1D1 in the progression of breast cancer, mammary gland tumor tissues were obtained from 14 weeks old FVB Nr1d1+/+;PyMT and Nr1d1-/-;PyMT mice and the gene expression patterns were analyzed by RNA-seq.
2023-06-27 | GSE222645 | GEO