To identify epigenetically silenced genes in multiple myeloma (MM) cell lines and to determine the effects of 5-aza-2-deoxycytidine and trichostatin A on gene expression. We treated 3 multiple myeloma cell lines (MM1, NCI-H929, U266) with 5-aza-2-deoxycytidine and/or trichostatin A.
Genome-wide transcriptional response to 5-aza-2'-deoxycytidine and trichostatin a in multiple myeloma cells.
Specimen part, Disease, Cell line
View Samplesusing RNA-seq we characterized gene expression changes occuring upon knockout of BAP1, ASXL1, ASXL2, ASXL1/2 or Polycomb genes RING1B and EZH2. We also investigated the response to retinoic acid treatment in wild-type and BAP1 KO cells. Overall design: Examination of transcript abundance in wild-type HAP1 cells and in 9 different HAP1-mutated cell lines as well as upon retinoic acid treatment in wild-type and BAP1 KO cells. Two biological replicated were performed for each condition.
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Cell line, Treatment, Subject
View SamplesCharacterization of gene expression changes occuring upon knockout of RING1A, RING1B, and BAP1. Overall design: Four Samples
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide CpG island methylation analyses in non-small cell lung cancer patients.
Specimen part, Disease, Cell line, Treatment
View SamplesEpigenetic changes largely contribute to the regulation of gene expression in cancer cells. DNA methylation is part of the epigenetic gene regulation complex which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stage I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis using NimbleGens 385K Human CpG Island plus Promoter arrays. By testing for differences in methylation between tumors and corresponding non-malignant lung tissues, we identified 298 tumor-specifically methylated genes. From many of these genes epigenetic regulation was unknown so far. Gene Ontology analysis revealed an over-representation of genes involved in regulation of gene expression and cell adhesion. Expression of 182 of 298 genes was found to be upregulated after 5-aza-2-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) treatment of 3 NSCLC cell lines by Affymetrix microarray analysis. In addition, methylation of selected genes in primary NSCLCs and corresponding non-malignant lung tissue samples were analyzed by methylation-sensitive high resolution melting analysis (MS-HRM). Our results obtained by MS-HRM analysis confirmed our data obtained by MeDIP-chip analysis. Moreover, by comparing methylation results from MeDIP-chip analysis with clinico-pathological parameters of the patients we observed methylation of HOXA2 as potential parameter for shorter disease-free survival of NSCLC patients. In conclusion, using a genome-wide approach we identified a large number of tumor-specifically methylated genes in NSCLC patients. Our results stress the importance of DNA methylation for the pathogenesis of NSCLCs.
Genome-wide CpG island methylation analyses in non-small cell lung cancer patients.
Cell line, Treatment
View SamplesUsing RNA-seq we characterized gene expression changes occuring upon knockout of EZH2, EZH1, EZH1+EZH2 or SUZ12 in a neurofibroma cell line. We also investigated the transcriptional consequences of EZH1+EZH2 double knockout in a SUZ12-mutant MPNST cell line. Overall design: Examination of transcript abundance in wild-type and mutant ipNF05.5 or 88.14 cells. Two biological replicates were performed for wild-type and mutant ipNF05.5 cell lines. Three biological replicates were performed for wild-type and mutant 88.14 cell lines.
EZH1/2 function mostly within canonical PRC2 and exhibit proliferation-dependent redundancy that shapes mutational signatures in cancer.
Cell line, Subject
View SamplesIL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: Examination of DMF-induced expression changes in 3 conditions, 3 samples each: murine TC17 cells without treatment as control group, murine Tc17 cells treated with DMF and murine Tc17 cells treated with DMF and Glutathione(GSH)
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Specimen part, Cell line, Subject
View SamplesIL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: CD8+ memory cells from human blood
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.
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