Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Rintaro Hashizume
PROVIDER: E-GEOD-59497 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:ChIP-Seq analysis of a pediatric human diffuse intrinsic pontine glioma (DIPG) cell line SF8628, harboring the K27M mutation. Goal was to obtain quantitative estimates of K27me3 immunoprecipitation change between vehicle-treated SF8628 cells [dimethyl sulfoxide, (DMSO)] and SF8628 cells incubated with 6 mM GSKJ4 at 24 hours and 72 hours. Three-condition experiment: 72 h GSKJ4-treated cells vs. 24 h GSKJ4-treated cells vs. DMSO-treated cells. Biological replicates: 1 cell line, each with 2 technical replicates per condition.
2014-07-20 | E-GEOD-59496 | biostudies-arrayexpress
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2012-05-31 | E-GEOD-33725 | biostudies-arrayexpress
Project description:Soybean toxin (SBTX) is an antifungal protein from soybeans with broad growth and filamentation inhibitory activity against many fungi, including human and plant pathogenic species such as Candida albicans, Candida parapsilosis, Aspergillus niger, Penicillium herquei, Cercospora sojina, and Cerospora kikuchii. Understanding the mechanism by which SBTX acts on fungi and yeasts may contribute towards the design of novel antifungal drugs and/or for the development of transgenic plants resistant to pathogens. To gain new insights into the mode of action of SBTX, the polymorphic yeast C. albicans was chosen as a model organism, and changes in the gene expression profile of strain SC5314 upon exposure to SBTX were examined. Genes that were differentially regulated in the presence of SBTX were involved in glucose transport and starvation-associated stress responses, as well as in the control of both the induction and repression of C. albicans hyphal formation. Transmission electron microscopy showd that C. albicans cells exposed to SBTX displayed severe signs of starvation and were heavily granulated. Our data were indicative of C. albicans cells starving despite sufficient nutrient availability in the medium, and it can therefore be speculated that SBTX blocks nutrient uptake systems. Because neither the starvation signal nor the alkaline response pathway lead to the induction of hyphae, we hypothesise that conflicting signals are transmitted to the complex regulatory network controlling morphogenesis, eventually preventing the filamentation signal from reaching a significant threshold. For transcriptional profiling, the cells were growth in the presence or absence of SBTX (200 M-BM-5gM-bM-^HM-^YmL-1) in SDB/4.The cultures were grown until they reached an OD600 of approximately 0.5, after 16 and 18 h, for untreated and SBTX-treated cells. The cells were harvested by centrifugation (3000M-bM-^@M-"g at 25M-BM-0C), snap-frozen in liquid nitrogen and stored at -80M-BM-0C. Each pair of samples (untreated and SBTX-treated cells) constituted a single experiment, and two biologically independent experiments were carried out.
2013-12-31 | E-GEOD-47364 | biostudies-arrayexpress
Project description:The master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit the Mediator co-activator to activate much of the gene expression program of embryonic stem cells (ESCs). We report here that the ESC master transcription factors and Mediator form M-bM-^@M-^\super-enhancersM-bM-^@M-^] at most genes known to control the pluripotent state, including those encoding the master transcription factors themselves. These super-enhancers consist of extraordinarily large genomic domains occupied by exceptional amounts of Oct4, Sox2, Nanog, Klf4, Esrrb and Mediator. Super-enhancers stimulate considerably higher transcription than typical enhancers in vivo and in reporter vectors. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. These results implicate super-enhancers in the control of mammalian cell identity and differentiation. Time-course of gene expression following shRNA knockdown of Oct4 and Med12.
2013-02-13 | E-GEOD-44287 | biostudies-arrayexpress
Project description:Background and Rationale: Factor VII activating protease (FSAP) is a circulating serine protease produced in the liver. A single nucleotide polymorphism (G534E, Marburg I, MI-SNP) in the gene encoding FSAP (HABP2) leads to lower enzymatic activity and is associated with enhanced liver fibrosis. FSAP is activated by damaged cells and its substrates include growth factors and haemostasis proteins. We have investigated the progression of liver fibrosis in FSAP deficient mice. Results: Wild type (WT) or FSAP-/- mice were subjected to bile duct ligation (BDL) and assessment of liver fibrosis. FSAP-/- mice showed enhanced liver fibrosis and accumulation of extracellular matrix as determined by Sirius Red staining and hydroxyproline content. FSAP deficient mice exhibited stronger injury as determined by higher necrosis in the liver and circulating liver enzymes. This correlated with expression of markers like M-NM-1-smooth muscle actin, collagen and fibronectin that are markers of stellate cell activation. FSAP-deficient mice exhibited higher expression of PDGF-BB as well as PDGFRM-NM-2 that are strong activators of liver fibrosis. In order to gain more insight into this difference microarray analysis was performed and the pattern of gene expression in WT vs. FSAP-/- mice would indicate that FSAP modulates the inflammatory /immune system. Conclusions: The results with FSAP-/- mice correlates with the human situation where lower FSAP activity, due to the MI SNP, is associated with enhanced liver fibrosis. This strengthens the concept that FSAP is a M-bM-^@M-^\protective factorM-bM-^@M-^] in liver fibrosis. A probable mechanism for this effect is likely to be related to the role of FSAP in the regulation of fibrosis/ inflammation-related processes n the liver. The dataset comprises 12 samples divided into four sample groups each representing a certain treatment group.
2012-09-19 | E-GEOD-36066 | biostudies-arrayexpress
Project description:The hallmark of follicular lymphoma (FL) is the t(14;18) chromosomal translocation. However, constitutive expression of anti-apoptotic Bcl-2 alone is insufficient for lymphomagenesis and subsequent molecular hits are required. We explored the role of microRNA (miRNA or miR) in the biology of FL by generating miRNA profiles of enriched sorted grade 1 and 2 FL tumor cells derived from 18 patients compared with enriched germinal center B-cells derived from seven follicular hyperplasia (FH). Expression levels of 851 human miRs were assayed and 133 miRs were significantly differentially expressed in FL tumor cells. The expression of 44 miRs in three major groups generated a unique FL signature. MiRs in group 1 were increased in FL (miR-193-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471). Group 2 was increased in the majority of FL cases but showed lower levels of expression in a subset of FL (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -451, -454, -502-3p, -532-3p, -574-3p, -664*, -1274a, -1274b, and -1260). MiR group 3 was decreased in FL (miR-17*, -30a, 33a, 106a*, -141, 202, -205, -222, 301b, -431*, and -570). Two patterns within FL were detected, largely due to the variable expression of group 2 miRs. The pattern with higher expression of group 2 miRs was associated with complete response to chemotherapy. Gene expression analysis of 199 genes related to lymphoma and tumor development performed in tandem indicated differential expression of 47 genes in FL including increased expression of AKT-1, PRKCE, IL4R, DROSHA, and MAPK1; and decreased expression of CHEK1, RAD51, CDKN1A, SOCS2, KLF4, BLIMP1 and IRF4. Functional studies provide evidence that miR-20a and -20b target CDKN1A/p21, miR-194 targets SOCS2, and miR-301b targets MAPK1 in FL, affecting cell proliferation and potentially contributing to lymphomagenesis. These findings suggest a role for aberrant miRNA expression in the biology of FL with prognostic and mechanistic implications. miRNA profiling was performed using Agilent miRNA array platform with RNAs isolated from sorted follicular lymphoma B cells and follicular hyperplasia B cells.
2012-05-02 | E-GEOD-28090 | biostudies-arrayexpress
Project description:A novel two-component system (TCS) DraR-K was identified previously to play a differential role in antibiotic biosynthesis (ACT, RED and yCPK) of Streptomyces coelicolor M145 on defined minimal medium (MM) conditions. In order to assess whether DraR-K has more global roles, a genome-wide transcriptomic analysis of the wild-type strain M145 and M-bM-^HM-^FdraR-K under the condition of 75 mM glutamine-based MM was performed using DNA microarray. The analysis demonstrated that deletion of draR-K led to the differential expression not only of the biosynthetic gene clusters of ACT, RED and yCPK, but also of other six secondary metabolite biosynthetic clusters, revealing the widely differenital regulation of DraR-K on secondary metabolism of S. coelicolor. Besides, a number of primary metabolism-related genes in the M-bM-^HM-^FdraR-K mutant, such as ureA/B/C/D/G/F, pstSCAB operon and chb gene also exhibited altered expression, which might enable the rebalance of C/N/P ratio under the condition of high concentration of Gln. We also observed that expression of many developmental genes (chpA/B/D/E, ramR/S and rdlA/B) was affected as well after draR-K deletion. Furthermore, the direct role of DraR-K on the transcription of several genes, including cdaR (the pathway-specific activator gene for CDA biosynthesis), chb, and pepA/pepA2 (SCO7336/7337, possibly involved in aerial mycelium development) were validated by electrophoresis mobility shift assays (EMSAs). In summary, our transcriptome analyses revealed the global regulation of DraR-K on physiological and morphological differentiation, especially its differential roles on secondary metabolism of S. coelicolor. The global transcription profiles of M145 and the M-bM-^HM-^FdraR-K mutant was compared using DNA microarray. RNA samples were isolated from these two strains grown on MM supplemented with 75 mM glutamine as the sole nitrogen source at three time points, 36, 48 and 60 h.
2014-03-10 | E-GEOD-55714 | biostudies-arrayexpress
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2012-03-06 | E-GEOD-28628 | biostudies-arrayexpress
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2014-10-23 | E-GEOD-54708 | biostudies-arrayexpress
Project description:The processing of seafood for human or animal consumption creates vast amounts of by-product, which is often considered waste. Although some of these by-products are used as fishmeal, bone-meal or fertilizer, as a whole, it remains under utilized. Significant amounts of proteins, lipid fractions, vitamins, and other bioactive molecules are present in these by-products, all with potential beneficial properties that could be used as alternatives to fishmeal or as supplements for aquaculture species. In an attempt to investigate their potential benefit in Atlantic salmon fish nutrition, nine experimental diets were formulated using by-products originating from various seafood processing plants. A control basal diet (no by-product added) was also formulated. Juvenile Atlantic salmons were fed one of the nine experimental diets (30% marine by-product, 70% basal diet) or the basal diet and hepatic gene expression profiling was done on fish fed each diet after 14 and 56 days. Analysis of hepatic gene expression revealed a significant amount of differentially expressed genes for each diet with roles in various pathways and biological processes. By comparing differences in hepatic gene expression levels with the nutritional composition of the various feeds, we were able to identify a number of nutritional elements that affect specific gene families. This information will be very useful for the formulation of novel fish feeds, which may be designed with specific aims, such as rapid growth, increased immunity or better general health This specific study is aimed at evaluating the hepatic transcriptional responses in juvenile Atlantic salmon fed with fish feed formulation supplemented with one of nine marine by-products.
2012-12-31 | E-GEOD-41325 | biostudies-arrayexpress