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SRP047459
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
- 99 Downloadable Samples
- Illumina HiSeq 2500
Description
Characterization of the transcriptome of normal and abnormal embryos. Overall design: Gene expression profiling of every mono and trisomy.
Publication Title
Human blastocysts of normal and abnormal karyotypes display distinct transcriptome profiles.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pirin (PIR) is a putative transcriptional regulator whose expression is silenced in cells bearing the AML1/ETO and PML/RAR leukemogenic fusion proteins and is significantly repressed in a large proportion of acute myeloid leukemias. PIR expression increases during in vitro myeloid differentiation of primary hematopoietic precursor cells, and ablation of PIR in the U937 myelomonocytic cell line or in murine primary hematopoietic precursor cells results in impairment of terminal myeloid differentiation.
Publication Title
Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profiles in blasts from three APL patients expressing PML/RAR were assessed before and after treatment with 1 uM retinoic acid (RA) in vitro for four hours. We then studied a U937 clone conditionally expressing PML/RAR (U937-PR), (Grignani et al. 1993) (Alcalay et al. 2003), and compared the gene expression profile prior to and after 4 hours of treatment with 1 uM RA, to that obtained from a cell line bearing an empty vector (U937-MT). For each sample, biotinylated cRNA targets were synthesized starting from 5ug of total RNA, and hybridized to the complete set of HG-U133 Affymetrix oligonucleotide chips, which explores the expression of approximately 45,000 human transcripts. Results were analyzed using MASv5 and further elaborated with the GenePicker software. GeneChip probe sets regulated by RA in each sample were clustered into non-redundant regulated genes according to UniGene release Hs.166.
Publication Title
Molecular signature of retinoic acid treatment in acute promyelocytic leukemia.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject, Compound
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We have analyzed 2 normal B cells isolated from peripheral blood and 5 CLL specimens with affy 133A microarray for expression.
Publication Title
Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene silencing in chronic lymphocytic leukemia cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant pulmonary epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of unselected cells. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8-weeks post-selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short term assays and enhanced outgrowth of premalignant lesions in longer term assays, thus overcoming important aspects of metastatic inefficiency. Overall, our findings indicate that among premalignant pulmonary epithelial cells, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior.
Publication Title
Identification of a Human Airway Epithelial Cell Subpopulation with Altered Biophysical, Molecular, and Metastatic Properties.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PU.1 is a key transcription factor for macrophage differentiation. Novel PU.1 target genes were identified by mRNA profiling of PU.1-deficient progenitor cells (PUER) before and after PU.1 activation. We used two different types of Affymetrix DNA-microarrays (430 2.0 arrays and ST 1.0 exon arrays) to characterize the global PU.1-regulated transcriptional program underlying the early processes of macrophage differentiation.
Publication Title
Transcriptomic profiling identifies a PU.1 regulatory network in macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mecp2 loss-of-function has been associated with altered gene expression in many tissues. We characterized gene expression changes within the hippocampi of 3 different Mecp2 loss-of-function mouse models.
Publication Title
An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders.
Sample Metadata Fields
Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Classic ‘position effect’ experiments repositioned genes to the telomere to demonstrate that the epigenetic landscape can dramatically alter gene expression. Here we show that systematic gene knockout collections provide an exceptional resource for interrogating position effects, not only at the telomere but at every single genetic locus. Because deleted genes are replaced by the same reporter gene, interrogation of this reporter provides a sensitive probe into many different chromatin environments while controlling for genetic context. Using this approach we find that, whereas replacement of yeast genes with the kanMX marker does not perturb the chromatin landscape, differences due to gene position account for more than 35% of marker gene activity. We observe chromatin influences different from those reported previously, including an antagonistic interaction between histone H3 lysine 36 trimethylation (H3K36me3) and the Rap1 transcriptional activation site in kanMX that is mediated through a Set2-Rpd3-dependent pathway. This interaction explains why some yeast genes have been resistant to deletion and allows successful generation of these deletion strains using a modified transformation procedure. These findings demonstrate that chromatin regulation is not governed by a uniform ‘histone code’, but by specific interactions between chromatin and genetic factors. Overall design: Data included are RNA-Seq data for 4 heterzygous diploid yeast strains and diploid wild-type. Therea re three replicates for each heterzygous strain, and six replicates for wild-type.
Publication Title
Decoupling epigenetic and genetic effects through systematic analysis of gene position.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Silver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that the majority of surfactant coated silver nanoparticles are not taken up into differentiated Caco-2 cells. and probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response.
Publication Title
Molecular mechanism of silver nanoparticles in human intestinal cells.
Sample Metadata Fields
Cell line
View Samples