Filters
Technology
Platform
GSE46016
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioblastoma (GBM) is thought to be driven by a sub-population of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity, yet remain poorly understood. Here we present a comparative epigenomic analysis of GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for maintenance and in vivo tumorigenicity of GBM CSCs. Genomewide binding profiles for ASCL1 and the Wnt effector LEF1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections between ASCL1, Wnt signaling and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs.
Publication Title
An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
We show that EWS-FLI1, an aberrant transcription factor responsible for the pathogenesis of Ewing sarcoma, reprograms gene regulatory circuits by directly inducing or directly repressing enhancers. At GGAA repeats, which lack regulatory potential in other cell types and are not evolutionarily conserved, EWS- FLI1 multimers potently induce chromatin opening, recruit p300 and WDR5, and create de novo enhancers. GGAA repeat enhancers can loop to physically interact with target promoters, as demonstrated by chromosome conformation capture assays. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors and abrogating p300 recruitment. Overall design: Ewing sarcoma cell lines (A673 and SKNMC) were analyzed by RNA-seq. EWS-FLI1 was depleted by infection with lentiviral shRNAs (shFLI1 and shGFP control).
Publication Title
EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Interferon-γ Inhibits Ebola Virus Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFN) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFN-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFN treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFN treatment inhibits genome replication. As IFN treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
Publication Title
Interferon-γ Inhibits Ebola Virus Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFN) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFN-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFN treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFN treatment inhibits genome replication. As IFN treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
Publication Title
Interferon-γ Inhibits Ebola Virus Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 137 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We obtained gene experssion profiles of 52 newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Publication Title
Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono-ubiquitination.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Rnf20 catalyzes lysine 120 mono-ubiquitination of histone H2B (H2Bub1) that has been previously involved in normal differentiation of embryonic stem (ES) and adult stem cells. However, the mechanisms underlying by which Rnf20 is recruited to its target chromosomal loci to generate H2Bub1 are still elusive. Here, we reveal that Fbxl19, a CxxC domain-containing protein, physically interacts with Rnf20, guides it preferentially to CpG island-containing target promoters, and thereby promotes mono-ubiqutination of H2B. We first show that up-regulation of Fbxl19 induces the level of global H2Bub1, while down-regulation of Fbxl19 reduces the level of H2Bub1 in mouse ES cells. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further show that the binding of Fbxl19 is essential for the recruitment of Rnf20 to its target genes and subsequent H2Bub1. Altogether, our results demonstrate that Fbxl19 plays critical roles in the H2Bub1 pathway by recruiting Rnf20 to CGI target genes specifically and selectively.
Publication Title
Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono-ubiquitination.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 2000
Description
We sought to more precisely characterize the different alpha-synuclein (aSyn) 3’UTR mRNA species in normal and PD human brain. High-throughput, whole-transcriptome sequencing of the 3’UTR ends of polyadenylated mRNA transcripts (termed pA-RNAseq; see Methods) was performed on a cohort of 17 unaffected and 17 PD cerebral cortical tissue samples. This revealed 5 aSyn 3’UTR isoforms, with lengths of 290, 480, 560, 1070 and 2520 nt. Of these, the 560 nt and 2520 nt forms were predominant. The existence and relative preponderance of these species was further confirmed by Northern Blot. We next hypothesized, that aSyn 3’UTR selection might be altered in PD. Comparison of pA-RNAseq profiles from PD and unaffected cerebral cortex samples revealed an increase in the preponderance of the long 3’UTR species (>560 nt) relative to shorter species (<560 nt). Such a relative increase in aSynL was confirmed by Quantitative real-time RT-PCR (rt-qPCR) and appeared specific for PD, as the increase was also observed by comparison to RNA from amyotrophic lateral sclerosis patient samples. We note that the modified aSyn 3’UTR selection associated with PD patient tissue was detected in cerebral cortex tissue, which typically harbors pathological evidence of the disease process without frank cell loss; thus, this phenotype is unlikely to be a secondary consequence of neurodegeneration. Overall design: Comparison of 3''UTR ends of alpha-synuclein in PD and unaffected brain cortex
Publication Title
Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples