Dnmt2 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 SamplesIdentify differentially expressed genes related to the neurodegenerative process in a new animal model of hepatic encephalopathy (HE).
Cerebellar neurodegeneration in a new rat model of episodic hepatic encephalopathy.
Specimen part, Treatment
View SamplesCyclin D3 is critical hematopoiesis and loss of cyclin D3 leads to resistance to transformation of bone marrow progenitors by Notch1-IC.
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.
Specimen part, Cell line
View SamplesActivated NOTCH1 induces T-ALL in mice when transduced in bone marrow (BM) cells. T-ALL cells activate the calcineurin/NFAT pathway in vivo (Medyouf H. et al. Nat Med 2007 [PMID 17515895]).
Leukemia-initiating cell activity requires calcineurin in T-cell acute lymphoblastic leukemia.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Specimen part, Treatment
View SamplesThe unfolded protein response (UPR) maintains endoplasmic reticulum (ER) proteostasis through the activation of transcription factors such as XBP1s and ATF6. The functional consequences of these transcription factors for ER proteostasis remain poorly defined. Here, we describe methodology that enables orthogonal, small molecule-mediated activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the same cell independent of stress. We employ transcriptomics and quantitative proteomics to evaluate ER proteostasis network remodeling owing to the XBP1s and/or ATF6 transcriptional programs. Furthermore, we demonstrate that the three ER proteostasis environments accessible by activating XBP1s and/or ATF6 differentially influence the folding, trafficking, and degradation of destabilized ER client proteins without globally affecting the endogenous proteome. Our data reveal how the ER proteostasis network is remodeled by the XBP1s and/or ATF6 transcriptional programs at the molecular level and demonstrate the potential for selectively restoring aberrant ER proteostasis of pathologic, destabilized proteins through arm-selective UPR-activation.
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Specimen part, Treatment
View SamplesThe unfolded protein response (UPR) maintains endoplasmic reticulum (ER) proteostasis through the activation of transcription factors such as XBP1s and ATF6. The functional consequences of these transcription factors for ER proteostasis remain poorly defined. Here, we describe methodology that enables orthogonal, small molecule-mediated activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the same cell independent of stress. We employ transcriptomics and quantitative proteomics to evaluate ER proteostasis network remodeling owing to the XBP1s and/or ATF6 transcriptional programs. Furthermore, we demonstrate that the three ER proteostasis environments accessible by activating XBP1s and/or ATF6 differentially influence the folding, trafficking, and degradation of destabilized ER client proteins without globally affecting the endogenous proteome. Our data reveal how the ER proteostasis network is remodeled by the XBP1s and/or ATF6 transcriptional programs at the molecular level and demonstrate the potential for selectively restoring aberrant ER proteostasis of pathologic, destabilized proteins through arm-selective UPR-activation.
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sex, Age, Specimen part, Disease
View SamplesGene expression profiling of liver biopsies collected from 33 healthy liver donors ranging from 13 to 90 years old. The Affymetrix HG-U133 Plus 2.0 GeneChip platform was used to evaluate gene-expression.
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sex, Age, Specimen part, Disease
View SamplesWe introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multigenerationa lineage tracking under controlled culture conditions. Overall design: Examination of lineage and cell cycle dependent transcriptional profiles in two cell types
A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.
Specimen part, Cell line, Subject
View Samples