During meiosis in yeast, global splicing efficiency increases. The mechanism for this is relief of competition for the splicing machinery by repression of intron-containing ribosomal protein genes (RPGs). Repression of RPGs with rapamycin also increases splicing efficiency in vegetative cells. Reducing levels of an RPG-dedicated transcription factor globally improves splicing and suppresses the temperature-sensitive growth defect of a spliceosome mutation. These results indicate that the spliceosome is limiting and pre-mRNAs compete with each other. Under these conditions, splicing efficiency of a given pre-mRNA therefore depends on both its concentration and affinity for the limiting splicing factor(s) as well as those of the competing pre-mRNAs. We propose that trans-competition control of splicing helps repress meiotic gene expression in vegetative cells, and promotes efficient meiosis. Competition between RNAs for a limiting factor may be a general condition important for function of a variety of post-transcriptional control mechanisms. Overall design: Splicing and gene expression profiles of 1) wild type yeast cells treated with rapamycin (2 biological replicates) relative to untreated cells and 2) prp4-1 pGAL-IFH1 (down-regulated expression of IFH1 transcription factor(specific for ribosomal protein genes)) relative to prp4-1 yeast.
Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing.
Treatment, Subject
View SamplesPyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds.
Transcriptional response of rat frontal cortex following acute in vivo exposure to the pyrethroid insecticides permethrin and deltamethrin.
Sex, Specimen part
View SamplesHsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells.
Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells.
Specimen part, Treatment
View SamplesMultiple myeloma is a fatal hematological malignancy. In order to develop effective therapeutic approaches, it is critical to understand the pathogenesis of myeloma. The Radl 5T model of multiple myeloma is a clinically relevant murine model where myeloma spontaneously occurs in aged, in-bred C57BlKalwRij mice and can be propagated by intravenous inoculation of 5T myeloma cells into mice of the same strain. Importantly inoculation of 5T myeloma cells into C57Bl6 mice does not result in myeloma, demonstrating that the bone marrow (BM) microenvironment of the C57BlKalwRij strain provides a unique and permissive milieu for myeloma development. We hypothesized that cells of the BM microenvironment may provide essential stimuli for the development of multiple myeloma in vivo. We aim to determine the differences in expression within the bone marrow of C57Bl/KalwRij mice.
Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease.
No sample metadata fields
View SamplesGene Expression profiling of the Arabidopsis thaliana MAP Kinase Kinases 1 (mkk1), MAP Kinase Kinases 2 (mkk2) knockout mutants and the double mutant mkk1/mkk2 before and 24 hours after treatment with the salicylic acid analog BTH, was measured by hybridisation to an Affymetrix ATH1 GeneChip.
Arabidopsis mitogen-activated protein kinase kinases MKK1 and MKK2 have overlapping functions in defense signaling mediated by MEKK1, MPK4, and MKS1.
No sample metadata fields
View SamplesTo dissect the functions of syndecan-1 in the nucleus, and separate them from functions related to the cell-surface, we transfected fibrosarcoma cells with two constructs: one encoding the full-length syndecan-1, which translocates to the nucleus and another encoding syndecan-1 lacking the RMKKK nuclear localization signal with hampered nuclear translocation.
Molecular targets and signaling pathways regulated by nuclear translocation of syndecan-1.
Specimen part, Cell line
View SamplesWe aimed to investigate the function of syndecan-1 in tumor cell adhesion and migration, with special focus on the importance of its distinct protein domains, to better understand the structure-function relationship of syndecan-1 in tumor progression. We utilized two mesenchymal tumor cell lines which were transfected to stably overexpress full-length syndecan-1 or truncated variants: the 78 which lacks the extracellular domain except the DRKE sequence proposed to be essential for oligomerization, the 77 which lacks the whole extracellular domain, and the RMKKK which serves as a nuclear localization signal. Various bioassays for cell adhesion, chemotaxis, random movement and wound healing were studied. Furthermore we performed gene microarray to analyze the global gene expression pattern influenced by syndecan-1.
Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.
No sample metadata fields
View SamplesThe transcriptomic responses of syndecan-1 silencing in a human mesothelioma cell line was followed with microarray analysis. To project the transcriptome analysis on the full-dimensional picture of cellular regulation, we applied a novel method of network enrichment analysis which elucidated signalling relations between differentially expressed genes and pathways acting via various molecular mechanisms.
Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.
Cell line
View SamplesFracture healing is a highly complex regenerative process. The sheep is an important large-animal model for studying delayed fracture healing. Here we used next-generation sequencing (Illimuna GA IIx) for gene expression analysis (RNAseq) in two conditional groups - standard and delayed healing. In both groups sequential biopsies 7, 11, 14 and 21 days after surgery were collected from callus tissue and annalized. For all timepoints and conditions the samples were pooled (n=6), except for day 21 standard (n=5).
Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing.
No sample metadata fields
View SamplesTo investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down-regulation upon lack of the enzymes, which correlates with gene activity but not gene length. Furthermore, our data reveal a distinct subclass of genes with a strong requirement for topoisomerases. These genes are characterized by high transcriptional plasticity, chromatin regulation, TATA box presence, and enrichment of a nucleosome at a critical position in the promoter region, in line with a repressible/inducible mode of regulation. Single-gene studies with a range of genes belonging to this group demonstrate that topoisomerases play an important role during activation of these genes. Subsequent in-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation and elongation of PHO5, as well as the nuclear entrance of Pho4p. Finally, we provide evidence that topoisomerases are required to maintain the PHO5 promoter in a superhelical state, which is competent for proper activation. In conclusion, our results reveal a hitherto unknown function of topoisomerases during transcriptional activation of genes with a repressible/inducible mode of regulation
DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae.
No sample metadata fields
View Samples