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GSE120347
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Microarray gene expression profiling reveals that PHGDH inhibition by NCT-503 activates a metabolic stress response characterized by downregulation of cell cycle genes and induction of stress response genes.
Publication Title
Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Complement protein C1q is induced after injury in the brain and during Alzheimer's disease and has been shown to protect against amyloid-beta induced neuronal death. In this study, we used microarray approach to identify the pathways modulated by C1q that are associated with neuroprotection.
Publication Title
C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse models, are essential for the C1q-mediated protection against amyloid-β neurotoxicity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Analysis of transcriptional changes upon persistent heat stress with emphasis on epigenetically regulated genes
Publication Title
Epigenetic regulation of repetitive elements is attenuated by prolonged heat stress in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The macrophage-Brucella interaction is critical for the establishment of a chronic Brucella infection. Smooth virulent B. suis strain 1330 (S1330) prevents macrophage cell death. However, rough attenuated B. suis strain VTRS1 induces strong macrophage cell death. To further investigate the mechanism of VTRS1-induced macrophage cell death, microarrays were used to analyze temporal transcriptional responses of murine macrophage-like J774. A1 cells infected with S1330 or VTRS1.
Publication Title
Proinflammatory caspase-2-mediated macrophage cell death induced by a rough attenuated Brucella suis strain.
Sample Metadata Fields
Cell line, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
DNA topoisomerases release supercoils in DNA introduced during replication or transcription. How DNA topoisomerases impact transcription in the context of eukaryotic chromatin is poorly understood. In this study, using a floral stem cell model in Arabidopsis, we uncovered a role of TOP1 in Polycomb Group (PcG) protein-mediated histone lysine 27 trimethylation at, and transcriptional repression of, the stem cell maintenance gene WUSCHEL (WUS). The strong genetic interactions between a top1 mutant and mutations in PcG genes and the overwhelming enrichment of PcG targets among genes affected in expression in the top1a mutant revealed a role of TOP1 in PcG-mediated regulation. Intriguingly, not only the repression of some PcG target genes but also the expression of others requires TOP1. The mechanism that unifies the opposing effects of TOP1 on PcG target genes appears to lie in its role in decreasing nucleosome density. Genome-wide nucleosome mapping shows that TOP1 is required for the depletion of nucleosomes at regulatory regions of genes, which probably allows the binding of factors that either recruit PcG, as we show for AGAMOUS at the WUS locus, or counteract PcG-mediated regulation. This study uncovers a strong and previously unknown connection between TOP1 and PcG.
Publication Title
DNA topoisomerase I affects polycomb group protein-mediated epigenetic regulation and plant development by altering nucleosome distribution in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis.
Publication Title
MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
A case of transcriptional gene silencing, originally observed in tetraploid Arabidopsis plants, created an epiallele resistant to many mutations or inhibitor treatments that activate other suppressed genes. This raised the question about the molecular basis of this extreme stability.
Publication Title
Cooperation of multiple chromatin modifications can generate unanticipated stability of epigenetic States in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abnormal NF-kB2 activation has been reported in several types of human leukemia and lymphomas although the exact mechanisms and affected pathways are not clear. We have investigated these questions through the use of a unique transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma associated NF-kB2 mutant. Microarray analysis, verified at the RNA and protein level identified new downstream targets and confirmed established regulatory networks. 201 genes were significantly changed, with 126 being upregulated and 75 downregulated. Pathway analysis uncovered both known and unknown interactions between factors important in the development of human B cell lymphomas and multiple myeloma, including cyclins D1 and D2, TRAF1, CD27, BIRC5/survivin, IL-15 and IL-10. Critical roles for STAT3 and TNF receptors are highlighted. Six target genes of STAT3 were identified: cyclins D1and D2, IL-10, survivin, IL-21 and Blimp1. Interfering with STAT3 signaling induced apoptosis in multiple myeloma cell lines. Novel pathways for NF-kB2 are proposed that involve IL-10 and other genes in the differentiation of plasma cells, evasion of apoptosis and proliferation. These pathways were verified with publically available human microarrays. Several treatment strategies based on these findings are discussed.
Publication Title
NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer.
Publication Title
The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation.
Sample Metadata Fields
Treatment
View Samples- Arabidopsis thaliana
- 5 Downloadable Samples
Illumina HiSeq 2000
Description
RNA-directed DNA methylation (RdDM) is a transcriptional silencing mechanism mediated by small and long noncoding RNAs produced by the plant-specific RNA polymerases Pol IV and Pol V, respectively. Through a chemical genetics screen with a luciferase-based DNA methylation reporter, LUCL, we found that camptothecin, a compound with anti-cancer properties that targets DNA topoisomerase 1a (TOP1a) was able to de-repress LUCL by reducing its DNA methylation and H3K9 dimethylation (H3K9me2) levels. Further studies with Arabidopsis top1a mutants showed that TOP1a promotes RdDM by facilitating the production of Pol V-dependent long non-coding RNAs, AGONAUTE4 recruitment and H3K9me2 deposition at transposable elements (TEs). Overall design: 5 small RNA libraries were sequenced
Publication Title
DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis.
Sample Metadata Fields
Specimen part, Subject
View Samples