Genetic, functional and molecular features of glucocorticoid receptor binding
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Joseph Maranville
PROVIDER: E-GEOD-45640 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches. GR and NFkB ChIP-seq in lymphoblastoid cell lines treated with either dexamethasone or EtOH (vehicle for dexamethasone) for 1 hour.
2013-04-01 | E-GEOD-45638 | biostudies-arrayexpress
Project description:Mycobacterium smegmatis is a model non-pathogenic mycobacterium that is efficiently killed by macrophages. Here, we explore the role of NF-?B in the innate immune response, focusing in detail on the mechanisms of the first killing period (1-4h) of M. smegmatis which coincides with phagosome-lysosome fusion. We show that infection of macrophages with M. smegmatis induces an activation of NF-?B and this activation is required for killing since treatment of macrophages with NF-?B inhibitors or siRNA silencing of the NF-?B subunit p65 increases bacterial survival. NF-?B induced proteins were thus hypothesized to be essential during the first phase of M. smegmatis killing. We therefore identified, using RNA microarray, the genes that were regulated during infection in the absence and presence of NF-?B inhibitors. By subtraction this provided a list of pro-inflammatory proteins that were under the control of NF-?B and putatively involved in the killing response. Among these category of genes were those for lysosomal enzymes and membrane trafficking regulators, including Cathepsins, LAMP-2 and Rab34, are regulated by NF-?B. Moreover, inhibition of NF-?B signaling retarded the delivery of v-ATPase, LAMP-2, CtsZ and CtsH thereby impairing the maturation of mycobacterial phagosomes. Collectively; our data provide the first compelling evidence that the innate immune response via NF-?B activation is linked to phagosome fusion with lysosomes that is essential for killing of mycobacteria. Keywords: NFkB inhibitor treated vs untreated The study includes J774 macrophage cell lines which are infected with Mycobacterium smegmatis in the presence and absense of NFkB inhibitor SC-514.Total RNA was isolated from individual samples and each sample was hybridised to CodeLink Mouse whole genome bioarray slides.This study was intended to know the role of NFkB regulated genes in killing non-pathogenic mycobacteria during 4 hour post infection of macrophages.
2007-10-23 | E-GEOD-8999 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches. Total RNA obtained from lymphoblastoid cell lines treated with either dexamethasone or EtOH (vehicle for dexamethasone) for 2, 4, 8, 12, 16, or 24 hours.
2013-04-01 | E-GEOD-44248 | biostudies-arrayexpress
Project description:Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics.
2023-09-26 | PXD043982 | Pride
Project description:Identification and characterization of epigenetically silenced genes is very important for cancer research. Particularly, information of hypermethylated genes provides clues to understand roles of epigenetics in tumorigeneses, and genes frequently methylated in a tumor-specific manner can be used as tumor markers. DNA methylation inhibitors such as 5-aza-cytidine or 5-aza-2M-bM-^@M-^Y-deoxycytidine were widely used to search epigenetically silenced genes. However, these inhibitors frequently upregulate genes whose promoters remain unmethylated. We tried to improve the specificity and sensitivity in detecting such methylation-mediated silenced genes in cancer and successfully developed a new method termed M-bM-^@M-^\methyl-CpG targeted transcriptional activation (MeTA)M-bM-^@M-^] by using a transcriptional activating fragment with a methyl-CpG binding domain (MBD) that specifically recognizes and binds to methylated DNAs. Because MBD proteins in fact mediate transcriptional repression of tumor suppressor genes associated with promoter hypermethylation in cancer, MeTA is thought to be one of the ideal methods to search such genes. In the present study, we applied this method to three representative pancreatic cancer cell lines, AsPC-1, MIA PaCa-2, and PANC-1, with a normal pancreatic ductal epithelial cell line HPDE (as the control). All of these cell lines have already been analyzed their expression profiles by 5-aza-2M-bM-^@M-^Y-deoxycytidine. We first analyzed the expression of five genes by RT-PCR with Southern hybridization, NEFH, NPTX2, SFRP1, TIMP3, and UCHL1; these genes are known to be methylated in at least any one of these cancer cell lines. Upregulation by M-bM-^@M-^\MeTAM-bM-^@M-^] was confirmed in all of these genes. Then we searched for upregulated-genes, by two-folds or more, in all the three cancer cell lines after MeTA; nineteen such upregulated genes were identified. Among these, sixteen genes except NEFH, HOXA9, and CLDN5 have not been reported previously using the conventional DNA methylation inhibitors. Methylation status of two genes, SLC32A1 and CSMD2, were further analyzed by methylation-specific PCR and found that SLC32A1 and CSMD2 were methylated in 100% (21/21) and 83% (15/18) pancreatic cancer cell lines analyzed, respectively. Our results suggest that M-bM-^@M-^\MeTAM-bM-^@M-^] is a highly efficient method to isolate methylation-mediated transcriptionally silenced genes in human pancreatic cancer and that this method can be applied to other types of human cancer. Three representative pancreatic cancer cell lines, AsPC-1, MIA PaCa-2, and PANC-1, with a normal pancreatic ductal epithelial cell line HPDE (as the control) were transfected with pcDNA6/myc-His vector or pcDNA6-3xFLAG-NFkB (AD)-MBD and were harvested 48 h after transfection.
2012-12-11 | E-GEOD-26215 | biostudies-arrayexpress
Project description:Analysis of dexamethasone-regulation of muscle mass at gene expression level. The hypothesis tested in the present study was that the presence of MuRF1 contributes to the extent of gene expression changes observed in specific sets of genes during a challenge leading to muscle atrophy. Results provide important information on the response of triceps surae muscle to synthetic glucocorticoid treatment, such as specific cell signaling and metabolic enzyme genes, that may be influenced by MuRF1 during atrophy. Total RNA obtained from isolated triceps surae muscle subjected to 3 or 14 days dexamethasone treatment compated to untreated littermate control muscles.
2013-02-12 | E-GEOD-44208 | biostudies-arrayexpress
Project description:Extensive changes in post-translational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs), various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSC. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSC cells and plays a central role in controlling stem cell differentiation. This set contains 29 microarray samples and includes the following 5 conditions: undifferentiated hMSCs, 2 day osteoblast differentiation, 5 day osteoblast differentiation, 2 day adipocyte differentiation, and 5 day adipocyte differentiation. 3 siRNA control samples and 3 RNF40 knockdown samples for each condition (except two control siRNA samples for 2 days osteoblast differentiation).
2013-01-03 | E-GEOD-38173 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-12 | E-GEOD-44259 | biostudies-arrayexpress
Project description:we analyzed the expression level change of transcription factors in adipose derived stem cells during osteogenic differentiation and found a candidate target gene, Sox11. We defined that Sox11 suppresses osteogenic differentiation through overexpression and knock down of Sox11. total RNA obtained from adipose derived stem cells subjected to 1,3,6,10 or 14 days in osteogenic differentiation compared to undifferentiated control adipose derived stem cells.
2012-01-05 | E-GEOD-34842 | biostudies-arrayexpress
Project description:Human abdominal adipose tissue was obtained with informed consent from a 33-year old Caucasian female (BMI = 32.96 Kg/m2) undergoing lipoaspiration. Adipose stromal cells (hASCs) were isolated and differentiated into adipocytes in vitro. Two technical replicates from 9 time points relative to induction of adipogenesis (day 0). Also, one sample from pre-adipocytes (day -2) grown without FGF.
2010-09-30 | E-GEOD-20699 | biostudies-arrayexpress