Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE23659
PROVIDER: PRJNA133129 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss. Mouse Embryonic Fibroblasts (MEFs) conditionally inactivated for Ezh2, Snf5 and Ezh2, or from control WT MEFs were used to evaluated epigenetic antagonism between Snf5 and Ezh2 in the control of gene expression programs. Snf5-deficient lymphoma samples and control CD8+ WT T-cells were used to evaluate genetic programs misregulated by Snf5 inactivation during tumorigenesis. RNA was isolated from each of these samples and used for gene expression profiling on Affymetrix arrays.
2010-10-19 | E-GEOD-23656 | biostudies-arrayexpress
Project description:Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.
2010-10-19 | GSE23656 | GEO
Project description:Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.
2010-10-19 | GSE23658 | GEO
Project description:Epigenetic antagonism between Snf5 and Ezh2 during oncogenic transformation and elevated levels of H3K27me3 in Snf5-deficient cells
| PRJNA130857 | ENA
Project description:Epigenetic enhancer changes during oncogenic transformation
| PRJNA393898 | ENA
Project description:We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies.
2020-04-14 | GSE121709 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description: Not available
| S-EPMC11335981 | biostudies-literature
Project description:As a master regulator of chromatin structure and function, the EZH2 lysine methyltransferase orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non- small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 has proven elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with a new genetically-engineered mouse model of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor that arises from a facile synthesis and possesses improved pharmacologic properties. JQEZ5 promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a defined subset of lung cancer. Gene expression analysis of 7 samples, 3 EZH2 OE tumors, 2 EZH2 OE normal lung samples, and 2 WT lung samples
2015-11-01 | E-GEOD-70046 | biostudies-arrayexpress
Project description:Epigenetic enhancer changes during oncogenic transformation [RNA-seq]
| PRJNA393901 | ENA