Genome-wide analysis of gene expression perturbed by RORa in MEFs subjected to control and 12 hour DNA damaged condition.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE27983 | GEO | 2011/12/30
SECONDARY ACCESSION(S): PRJNA137811
REPOSITORIES: GEO
Similar Datasets
Project description:In order to investigate the role of RORa on the expression of damage responsive genes across the whole genome, we performed a microarray analysis from RNAs isolated from wild type MEFs or staggerer MEFs in control and damaged conditions. Wild type MEFs and staggerer MEFs were treated doxorubicin for 12 hours. Cells were then lysed and RNA isolated.
2011-12-30 | E-GEOD-27983 | biostudies-arrayexpress
Project description:The retinoic acid receptor-related orphan receptor a (RORa) is a member of the NR1 subfamily of orphan nuclear hormone receptors. RORa is an important regulator of various biological processes, including cerebellum development, cancer and circadian rhythm. To determine molecular mechanism by which hepatic deletion of RORa induces obesity and insulin resistance, we performed global transcriptome analysis from high-fat diet (HFD)-fed RORa f/f and RORa LKO mouse liver tissues. This analysis provides insight into molecular mechanisms for RORa in high-fat-diet condition.
2017-06-28 | GSE83338 | GEO
Project description:WT TR MEFs and Keap1–/– TR MEFs were established according to the following method. Keap1+/– mice were mated, and WT and Keap1–/– embryos were collected at embryonic day 13.5. Primary MEFs were immortalized by expression of SV40 T antigen. The immortalized MEFs were transformed by expression of HRAS G12V to generate WT TR MEFs and Keap1–/– TR MEFs.
2017-05-06 | GSE98594 | GEO
Project description:We performed RNAseq to identify mRNAs that were specifically down regulated in neutrophils when RORa function is inhibited
2021-04-06 | GSE171501 | GEO
Project description:Naive CD4 T cells were taken from spleens of wild-type mice, and activated with CD3/CD28. IL4 was added to induce Th2. The cells were transduced with retrovirus to overexpress RORA vs control. Three different viral constructs were tested. M6-Rora2_mCherry appear to give the best result based on RNAseq validation of Rora expression. Rora2 = ENSMUST00000113624
2019-06-10 | E-MTAB-8001 | biostudies-arrayexpress
Project description:Full development of IL-17 producing CD4+ T helper cells (TH17 cells) requires the transcriptional activity of both orphan nuclear receptors RORa and RORgt. Despite this evidence, RORa is considered functionally redundant to RORgt; thus, the function and therapeutic value of RORa in TH17 cells remains underexplored. Using mouse models of autoimmune and chronic inflammation, we show that expression of RORa is required for TH17 cell pathogenicity. T-cell specific deletion of RORa reduced the development of experimental autoimmune encephalomyelitis (EAE) and colitis. Reduced inflammation was associated with decreased TH17 cell development, lower expression of tissue-homing chemokine receptors and integrins, and increased frequencies of Foxp3+ T regulatory (Treg) cells. Importantly, inhibition of RORa with a selective small molecule antagonist largely phenocopied our genetic data, potently suppressing the in vivo development of both chronic/progressive and relapsing/remitting EAE but had no effect on overall thymic cellularity. Furthermore, use of the RORa antagonist effectively inhibited human TH17 cell differentiation and memory cytokine secretion. Together, these data suggest that RORa acts independently of RORgt in programming TH17 pathogenicity and identifies RORa as a safer and more selective therapeutic target for the treatment of TH17-mediated autoimmunity.
2020-10-29 | GSE160327 | GEO
Project description:RORasg/sg mice have small cardiomyocytes and hypocontractile hearts with increased fibrosis. Microarrays revealed broad deficits of sarcomeric RNAs and key myogenic transcription factors, suggesting that the loss of RORa leads to impaired developmental hypertrophy through transcriptional regulation. RORasg/sg mice developed exaggerated ventricular remodeling in response to Agn II infusion. We identify novel cardioprotective roles for RORa in promoting developmental and preventing pathological cardiac hypertrophy, mediated in part through regulation of the IL-6-STAT3 pathway in cardiomyocytes and cardiac fibrosis
2021-04-12 | GSE98892 | GEO
Project description:Background: We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Methods: Here we comprehensively identify transcriptional targets of RORA in human neuronal cells using chromatin immunoprecipitation (ChIP), followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then further validated by an independent chromatin immunoprecipitation, followed by qPCR analysis. To further demonstrate that reduced RORA expression results in aberrant transcription of RORA targets, we determined the expression levels of selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. Results: The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 1,338 genomic locations corresponding to promoter regions of 1,274 genes across the human genome. Among the genes potentially directly regulated by RORA1 are genes known to have biological functions negatively impacted in individuals with ASD, including neuronal adhesion and survival, synaptogenesis, and development of the cortex and the cerebellum. Independent ChIP-qPCR analyses confirm binding of RORA1 to promoter regions of several ASD-associated genes, including A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, whose expression levels are also decreased in RORA1-repressed human neuronal cells and in prefrontal cortex tissues from individuals with ASD. Conclusion: Findings from this study indicate that RORA transcriptionally regulates A2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1, and NTRK2, and strongly suggest that reduction of this sex hormone-sensitive nuclear receptor in the brain causes dysregulated expression of these genes which, in turn, may contribute to the underlying pathobiology of ASD. Nuclear lysates from the human neuroblastoma cell line SH-SY5Y were chromatin-immunoprecipitated with goat anti-RORA1 antibody vs. normal goat IgG antibody
2013-05-31 | E-GEOD-45756 | biostudies-arrayexpress
Project description:Distal regulatory elements, such as enhancers, play a pivotal role in dictating cell identity by controlling the transcriptional status of specific cells. The comprehensive understanding of the epigenetic landscape, encompassing enhancer establishment and chromatin accessibility, during the differentiation of human Th17 cells remains incomplete. Leveraging ATAC-seq based chromatin accessibility profile along with the profiling of key histone marks we identified potential enhancers crucial for fate specification of Th17 cells. We found that 24 single nucleotide polymorphisms (SNPs) associated with autoimmune diseases were located near Th17-enhancers. Interestingly, these SNPs overlapped the binding sites of transcription factor active in Th17 cells. Among the Th17 specific enhancers, we identified an enhancer in the intron of RAR-related orphan receptor alpha (RORA) that was earlier predicted to regulate RORA expression. Functional validation through luciferase reporter assays confirmed that this enhancer positively regulate the transcription. Moreover, employing CRISPR-Cas9-mediated deletion of a transcription factor binding site-rich region within the identified RORA enhancer, we demonstrated its role in regulating RORA transcription. These findings provide insights into the potential mechanism by which the RORA enhancer modulates Th17 differentiation and into the role of regulatory SNPs within noncoding regions in conferring resistance or susceptibility to Th17 cell-mediated autoimmune pathologies.
2024-05-23 | GSE243058 | GEO
Project description:Distal regulatory elements, such as enhancers, play a pivotal role in dictating cell identity by controlling the transcriptional status of specific cells. The comprehensive understanding of the epigenetic landscape, encompassing enhancer establishment and chromatin accessibility, during the differentiation of human Th17 cells remains incomplete. Leveraging ATAC-seq based chromatin accessibility profile along with the profiling of key histone marks we identified potential enhancers crucial for fate specification of Th17 cells. We found that 24 single nucleotide polymorphisms (SNPs) associated with autoimmune diseases were located near Th17-enhancers. Interestingly, these SNPs overlapped the binding sites of transcription factor active in Th17 cells. Among the Th17 specific enhancers, we identified an enhancer in the intron of RAR-related orphan receptor alpha (RORA) that was earlier predicted to regulate RORA expression. Functional validation through luciferase reporter assays confirmed that this enhancer positively regulate the transcription. Moreover, employing CRISPR-Cas9-mediated deletion of a transcription factor binding site-rich region within the identified RORA enhancer, we demonstrated its role in regulating RORA transcription. These findings provide insights into the potential mechanism by which the RORA enhancer modulates Th17 differentiation and into the role of regulatory SNPs within noncoding regions in conferring resistance or susceptibility to Th17 cell-mediated autoimmune pathologies.
2024-05-23 | GSE243062 | GEO