Dnmt2 genes are highly conserved tRNA methyltransferases with biological roles in cellular stress responses. The absence of obvious mutant phenotypes under laboratory conditions suggested a function for Dnmt2 under non-physiological conditions. Indeed, Dnmt2 has recently been implicated in various aspects of the cellular stress response and the tRNA methyltransferase activity of Dnmt2 has been shown to interfere with stress-induced fragmentation of various tRNAs. We used adult animals and small RNA sequencing during a heat stress experiment to determine the tRNA fragment abundance and identities in wild-type and Dnmt2 mutant somatic tissues. Dnmt2 mutants produced tRNA fragments with different identities when compared to wild-type controls, indicating the accumulation of non-physiological tRNA-derived molecules in tissues without Dnmt2. Overall design: 6 samples examined: heterozygous and Dnmt2 mutant under control, heat shock and recovery conditions
The RNA methyltransferase Dnmt2 is required for efficient Dicer-2-dependent siRNA pathway activity in Drosophila.
Specimen part, Cell line, Subject
View SamplesThis project is based on the hygiene hypothesis that exposure to TB provides a protective mechanism against asthma through specific cytokines and the balance of Th1, Th2 cells. Additionally, expression changes are examined in patients with and without atopy in combination with asthma and PPD status. Expression levels were evaluated in CD4+ cells isolated from peripheral blood of 30 patients. Each patient was evaluated on the entire U133 Affymetrix GeneChip set.
A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.
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View SamplesDnmt2 genes are highly conserved tRNA methyltransferases with biological roles in cellular stress responses. Dnmt2 has recently been implicated in transposon silencing in Drosophila but the exact molecular mechanisms are unclear. Adult Dnmt2 mutants were heat shocked and RNA sequencing was performed on visible high-molecular weight RNAs to determine the identity of up-regulated transposons. Dnmt2 mutants accumulated almost all families of transposons after heat shock, indicating a general mis-regulation of transposon silencing in Dnmt2 mutants during the stress response. Overall design: one sample, excised, electroeluted and pooled RNA of different molecular weight, Dnmt2 mutant during recovery from a single heat shock
Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats.
Sex, Specimen part, Cell line, Subject
View SamplesWe profiled and quantitated miRNAs in two skin tumors (Basal cell carcinoma and Merkel cell carcinoma) and identified tumor-specific miRNAs. We used these tumor-specific miRNAs to guide development of miRNA fluorescence in situ hybridization. Overall design: 2 barcoded sequencing runs, including 40 unique samples (36 used in manuscript). The details of each sample can be found in Supplementary Tables S1 and S2.
Multicolor microRNA FISH effectively differentiates tumor types.
Specimen part, Cell line, Subject
View SamplesCombined treatment with all-trans retinoic acid and GSK2879552 results in synergistic effects on gene expression, cell proliferation, markers of differentiation, and, most importantly, cytotoxicity. Overall design: Gene expression analysis of DMSO, single and combination treatment (ATRA and GSK2879552) on 6 AML cell lines at two time-points with two replicates (paired end RNA-seq on 96 samples in total)
Lysine specific demethylase 1 inactivation enhances differentiation and promotes cytotoxic response when combined with all-<i>trans</i> retinoic acid in acute myeloid leukemia across subtypes.
Cell line, Treatment, Subject
View SamplesPrimitive neuroectodermal tumors of the central nervous system (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children. Using DNA methylation and gene expression profiling we have demonstrated that a significant proportion of institutionally diagnosed CNS PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropiate therapy for children with these tumors. From the remaining fraction of CNS PNETs, we have identified four distinct new CNS tumor entities extending to other neuroepithelial tumors, each associated with a recurrent genetic alteration and particular histopathological and clinical features. These molecular entities, designated CNS Neuroblastoma with FOXR2 activation (CNS NB FOXR2), CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT CIC), CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET MN1), and CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET BCOR), will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by these poorly differentiated CNS tumors.
New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.
Sex, Age
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