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GSE52392
Homo sapiens
94 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 94 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
We used the Infinium HumanHT-12 platform to profile gene expression in 79 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 13 representative sarcoma cell lines.
Publication Title
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 90 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Here we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Publication Title
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Sample Metadata Fields
Time
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
GUN1 integrates retrograde signals in the chloroplast but the underlying mechanism is elusive. FUG1, a chloroplast translation initiation factor, and GUN1 are co-expressed at the transcript level, and FUG1 co-immunoprecipitates with GUN1. We used mutants of GUN1 (gun1-103) and FUG1 (fug1-3) to analyse their functional relationship at the physiological and systems-wide level, the latter including transcriptome and proteome analyses. Absence of GUN1 aggravates the effects of decreased FUG1 levels on chloroplast protein translation, resulting in transient additive phenotypes with respect to photosynthesis, leaf coloration, growth and cold acclimation. Variegation of the var2 mutant is enhanced by gun1-103 in terms of increasing the fraction of white sectors, in contrast to fug1-3 that acts as suppressor. The transcriptomes of fug1-3 and gun1-103 are very similar, but absence of GUN1 alone has almost no effects on protein levels, whereas chloroplast protein accumulation is markedly decreased in fug1-3. In gun1 fug1 double mutants, effects on transcriptomes and particularly proteomes are enhanced. Our results show that GUN1 function becomes critical when chloroplast proteostasis is perturbed by decreased translation (fug1) or degradation (var2) of chloroplast proteins. The functions of FUG1 and GUN1 appear to be related, corroborating the view that GUN1 operates in chloroplast proteostasis. Overall design: Examination of differential gene expression in the Arabdidopsis thaliana gun1, fug1 and gun1 fug1 mutants compared to wild type in three replicates
Publication Title
Relationship of GUN1 to FUG1 in chloroplast protein homeostasis.
Sample Metadata Fields
Subject
View Samples- Danio rerio
- 188 Downloadable Samples
- Affymetrix Genechip Zebrafish ST Genome Array 1.1 (zebgene11st)
Description
Zebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
Publication Title
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
Publication Title
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 550
Description
WT J1 and 3B3L cells (in which Dnmt3B and Dnm3L are constitutively expressed from an exogenous construct) were cultured under both serum/LIF and 2i/LIF conditions. 3B3L cells do not show ground state-associated hypomethylation phenotype. This experiment sought to analyse the gene expression changes between the two conditions. Overall design: Three biological replicates per condition J1 serum, J1 2i, 3B3-3l serum, 3B3-3l 2i.
Publication Title
DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
TFIID is a central player in activated transcription initiation. Recent evidence suggests that the role and composition of TFIID is more diverse than previously understood. To investigate the effects of changing the composition of TFIID in a simple system we depleted TAF1 from Drosophila cells and determined the consequences on metal induced transcription at an inducible gene, Metallothionein B (MtnB). We observe a marked increase in the levels of both the mature message and pre-mRNA in TAF1 depleted cells. Under conditions of continued metal exposure, we show that TAF1 depletion increases the magnitude of the initial transcription burst, but has no effect on the timing of that burst. We also show that TAF1 depletion causes delay in the shut-off of transcription upon removal of the stimulus. Thus TAFs are involved in both establishing an upper limit of transcription during induction and efficiently turning the gene off once the inducer is removed. Using genomewide nascent-seq we identify hundreds of genes that are controlled in a similar manner indicating that the findings at this inducible gene are likely generalizable to a large set of promoters. There is a long-standing appreciation for the importance of the spatial and temporal control of transcription. Here we uncover an important third dimension of control, the magnitude of the response. Our results show that the magnitude of the transcriptional response to the same signaling event, even at the same promoter, can vary greatly depending on the composition of the TFIID complex in the cell. Overall design: Nascent RNA was sequenced from replicate samples of Drosophila S2 cells treated with double-stranded RNA directed against E. coli LacI (Control) or against Drosophlia TAF1 (experimental). Reads per kilo-base per million (RPKM) was determined for each gene and the control and experimental samples were compared to determine the genes that were affected by the depletion of TAF1.
Publication Title
Holo-TFIID controls the magnitude of a transcription burst and fine-tuning of transcription.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Breast cancer is genetically heterogeneous, and recent studies have underlined a prominent contribution of epigenetics to the development of this disease. To uncover new synthetic lethalities with known breast cancer oncogenes, we screened an epigenome-focused short hairpin RNA library on a panel of engineered breast epithelial cell lines. Here we report a selective interaction between the NOTCH1 signaling pathway and the SUMOylation cascade. Knockdown of the E2-conjugating enzyme UBC9 (UBE2I) as well as inhibition of the E1-activating complex SAE1/UBA2 using ginkgolic acid impairs the growth of NOTCH1-activated breast epithelial cells. We show that upon inhibition of SUMOylation NOTCH1-activated cells proceed slower through the cell cycle and ultimately enter apoptosis. Mechanistically, activation of NOTCH1 signaling depletes the pool of unconjugated small ubiquitin-like modifier 1 (SUMO1) and SUMO2/3 leading to increased sensitivity to perturbation of the SUMOylation cascade. Depletion of unconjugated SUMO correlates with sensitivity to inhibition of SUMOylation also in patient-derived breast cancer cell lines with constitutive NOTCH pathway activation. Our investigation suggests that SUMOylation cascade inhibitors should be further explored as targeted treatment for NOTCH-driven breast cancer. Overall design: We treated MCF10A and NOTCH1 cells with either DMSO or ginkgolic acid 30 uM for 3 days. Two replicates have been analysed for each condition.
Publication Title
NOTCH1 activation in breast cancer confers sensitivity to inhibition of SUMOylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HiSeq 4000
Description
Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers. Overall design: RNA-seq samples for knockouts of BAF complex in the HAP1 cell line.
Publication Title
Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.
Sample Metadata Fields
Cell line, Subject
View Samples