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GSE64537
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ezh2 encodes for the catalyc unit of the PRC2 complex. RNAi-mediated suppressing of Ezh2 by two independent shRNAs promotes Em-myc lymphomagenesis in vivo.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer.
Sample Metadata Fields
Sex, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Weve undertaken a genome-wide approach to identify and test genes in fibroblasts that are both induced upon interaction with basal breast cancer cells in culture and upregulated in stromal cells from primary human breast cancers. Several of the upregulated genes encode secreted growth factors or cytokines. Using RNAi and a co-injection tumorigenicity assay, we determined that the majority of secreted factors selected for functional validation played significant, yet functionally diverse, roles in promoting tumorigenicity. Rather than a single major mediator, these results indicate multiple points of intervention to prevent fibroblasts from supporting basal breast cancer. Additionally, we show that breast cancer subtypes differ markedly in the expression of these and other stromally secreted proteins using data from microdissected stromal samples.
Publication Title
System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types.
Publication Title
Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The assembly of neural circuits involves multiple sequential steps such as the specification of cell types, their migration to proper brain locations, morphological and physiological differentiation, and the formation and maturation of synaptic connections. This intricate and often prolonged process is guided by elaborate genetic mechanisms that regulate each developmental event. Evidence from numerous systems suggests that each cell type, once specified, is endowed with a genetic program that directs its subsequent development. This cell intrinsic program unfolds in respond to, and is regulated by, extrinsic signals, including cell-cell and synaptic interactions. To a large extent, the execution of this genetic program is achieved by the expression of specific sets of genes that support distinct developmental processes. Therefore, a comprehensive analysis of the developmental progression of gene expression in synaptic partners of neurons may provide a basis for exploring the genetic mechanisms regulating circuit assembly.
Publication Title
Developmental Coordination of Gene Expression between Synaptic Partners During GABAergic Circuit Assembly in Cerebellar Cortex.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Recurrent Copy Number Variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a behavior trap phenotypea specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. Our findings indicate that 16p11.2 CNVs cause both brain and behavioral anomalies, providing new insight into human neurodevelopmental disorders.
Publication Title
Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism.
Sample Metadata Fields
Sex
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Epigenetic pathways regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. While chromatin alterations are, in principle, reversible and often amendable to drug intervention, the promise of targeting such pathways therapeutically has been hampered by our limited understanding of cancer-specific epigenetic dependencies. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukemia (AML) an aggressive hematopoietic malignancy often associated with aberrant chromatin states. By screening a custom shRNA library targeting known chromatin regulators in a genetically defined AML mouse model, we identify the bromodomain-containing protein Brd4 as a critical requirement for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust anti-leukemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation. Extensive evaluation of JQ1-sensitivity in primary human leukemia samples and in established cell lines revealed a broad activity of this compound against diverse AML subtypes. These effects are, at least in part, due to a requirement for Brd4 in maintaining Myc expression and promoting aberrant self-renewal. Together, our results indicate that Brd4 is a promising therapeutic target in AML and identify a small molecule that efficiently targets Myc. These findings also highlight the utility of RNAi screening as a discovery platform for revealing epigenetic vulnerabilities for direct pharmacologic intervention in cancer.
Publication Title
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Arabidopsis thaliana
- 1 Downloadable Sample
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The mutation in the budding yeast gene PCNA, pol30-8, as well as deletion of DOT1 (dot1), encoding the only histone H3 K79 methyltransferase in budding yeast, have been implicated in telomeric silencing. To further analyze these mutants, we used microarrays to study whether either pol30-8, dot1 or the double mutant leads to changes in gene expression levels when compared to isogenic wild-type strains.
Publication Title
A common telomeric gene silencing assay is affected by nucleotide metabolism.
Sample Metadata Fields
No sample metadata fields
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