Physiologically, Notch signal transduction plays a pivotal role in differentiation; pathologically, Notch signaling contributes to the development of cancer. Transcriptional activation of Notch target genes involves cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD), and NICD migration into the nucleus and assembly of a coactivator complex. Posttranslational modifications of the NICD are important for its transcriptional activity and protein turnover. Deregulation of Notch signaling and stabilizing mutations of Notch1 have been linked to leukemia development. We found that the methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1; also known as PRMT4) methylated NICD at five conserved arginine residues within the C-terminal transactivation domain. CARM1 physically and functionally interacted with the NICD-coactivator complex and was found at gene enhancers in a Notch-dependent manner. Although a methylation-defective NICD mutant was biochemically more stable, this mutant was biologically less active as measured with Notch assays in embryos of Xenopus laevis and Danio rerio. Mathematical modeling indicated that full but short and transient Notch signaling required methylation of NICD.
Site-specific methylation of Notch1 controls the amplitude and duration of the Notch1 response.
Cell line
View SamplesDN3, DN4 and DP cells were sorted from 3-4 week old WT and mice and subjected to transcriptome analysis
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Specimen part
View SamplesThe mouse Ikaros-deficient thymic lymphoma cell line T29 was transduced with an empty retrovirus (MigR1) or a retrovirus expressing an fusion proein between Ikaros1 and the ligand binding domain of the estrogen receptor. Cells trreated with ethanol or 4-hydroxy-tamoxyfen (4OHT) for 24h were profiled.
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Cell line
View SamplesLineage-negative thymocytes were cultured on OP9-DL1 stromal cells for 16h in the presence of DMSO or the gamma secretase inhibitor MRK-003. DN3 cells cells were then sorted and their transcriptome analyzed.
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Specimen part, Treatment
View SamplesThe mouse Ikaros-deficient thymic lymphoma cell line T29 was transduced with a retrovirus expressing an fusion protein between a dominant-negative form of Mastermind and the ligand binding domain of the estrogen receptor. Cells trreated with Ethanol or 4-hydroxy-tamoxyfen for 24h were profiled.
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Cell line
View SamplesThe mouse Ikaros-deficient thymic lymphoma cell line T29 was treated with a gamma-secretase inhibitor or vehicle (DMSO) for 36h and subjected to transcriptome analysis.
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Cell line
View SamplesDouble positive thymocytes (CD4+CD8+CD3lo) were sorted from 3-4-week old mice from Ikf/f CD4-Cre+ or Ikf/f CD4-Cre- mice (2 mice per genotype) and their transcriptome analyzed.
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
No sample metadata fields
View SamplesThe aim of the experiment was to visualize genes under the control of Ikaros during early T cell development. We used mice carrying floxed Ikaros alleles that were crossed with the Rosa26-CreERT2 mice, and which were injected with tamoxifen for 4 days. DN4 thymocytes were sorted from 4 mice (5-6 week-old) which are positive or not for the Rosa26-CreERT2 transgene.
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Specimen part
View SamplesArabidopsis plants were treated either with mock or MSB (0.2 mM of Menadione sodium bisulphite). <br></br>Tissue was sampled after 3, 6 and 24 hours.
Molecular analysis of menadione-induced resistance against biotic stress in Arabidopsis.
Age, Specimen part, Compound, Time
View SamplesNeurodegenerative brain disorders become more common in the aged. Most of these disorders are associated with or caused by selective death of certain neuronal subpopulations. The mechanisms underlying the differential vulnerability of certain neuronal populations are still largely unexplored and few neuroprotective treatments are available to date. Elucidation of these mechanisms may lead to a greater understanding of the pathogenesis and treatment of neurodegenerative diseases. Moreover, preconditioning by a short seizure confers neuroprotection following a subsequent prolonged seizure. Our goal is to identify pathways that confer vulnerability and resistance to neurotoxic conditions by comparing the basal and preconditioned gene expression profiles of three differentially vulnerable hippocampal neuron populations.
Gene expression changes after seizure preconditioning in the three major hippocampal cell layers.
No sample metadata fields
View Samples