Ixr1 is a transcriptional factor from Saccharomyces cerevisae with high affinity to cisplatin-DNA adducts through their two HMG-box DNA binding domains. Its transcriptional regulation is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Ixr1 function.
Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin.
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View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
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View SamplesRecent studies suggest that telomerase promotes cell growth by mechanisms that extend beyond the rescue of critically short telomeres. The in vitro model of mTert overexpressing MEFs recapitulates fundamental aspects of the growth-promoting effects of mTert in vivo. First, in Terc-proficient cells, mTert overexpression favors escape from replicative senescence and enhances anchorage-independent growth in response to oncogenic stress, which fits well with previous data showing that mTert overexpression promotes tumor formation. Second, in Terc-deficient cells, retroviral transduction with mTert results in a delayed onset of immortalization and impairs colony formation in response to oncogenic stress, which is in agreement with the inhibitory effect of mTert overexpression on tumorigenesis in a Terc null mouse background. To unravel the molecular targets of telomerase that impact on cell growth, we compared the transcriptome of MEFs, before and after mTert introduction. We found that ectopic expression of mTert was associated with detectable gene expression changes (greater than 1.5-fold; validated by qRT-PCR) of 26 transcripts. Analysis of the observed transcriptional changes indicates that ectopic expression of mTert suppresses in a coordinated manner functionally related genes with overlapping roles in growth arrest, resistance to transformation, and apoptosis. We show that the majority of the telomerase target genes are growth-inhibitory, transforming growth factor-beta (TGF-beta) -inducible genes and provide functional evidence for the potential of telomerase to abrogate TGF-beta -mediated growth inhibition. Thus, in line with the current view that the diversity of TGF-beta responses is not so much a consequence of the use of different signaling pathways but caused by different ways of reading the output from the same basic pathway, we propose that the telomerase status of a cell creates a gene expression pattern that determines how cells read growth inhibitory signals, among them signals propagated through the TGF-beta pathway.
Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling.
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View SamplesGene expression profile of acute myeloid leukemia.
Gene expression profile reveals deregulation of genes with relevant functions in the different subclasses of acute myeloid leukemia.
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View SamplesAnalysis of primary bovine aortic endothelial cells treated for 24 hours with TGF-beta 1 5 ng/ml. TGF-beta 1 has been shown to induce endothelial-to-mesenchymal transition (EndoMT) and to be implicated in differentiation of endothelial cells into smooth muscle-like cells as occurred in vascular neointimal formation.
LOXL4 is induced by transforming growth factor β1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling.
Specimen part
View SamplesPIF3 plays a role as repressor of photomorphogenesis in darkness. To identify PIF3-regulated genes that might be implementing this action, we have performed whole-genome expression analysis in the pif3 mutant.
Functional profiling identifies genes involved in organ-specific branches of the PIF3 regulatory network in Arabidopsis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
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View SamplesTranscription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and the NPC-associated THSC/TREX-2 complex.
A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
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View SamplesThe zebrafish heart remarkably regenerates after a severe ventricular damage followed by inflammation, fibrotic tissue deposition and removal concomitant with cardiac muscle replacement. We have investigated the role of the endocardium in this regeneration process. 3D-whole mount imaging in injured hearts revealed that GFP-labelled endocardial cells in ET33mi-60A transgenic fish become rapidly activated and highly proliferative at 3 days post cryoinjury (dpci). Endocardial cells extensively expand within the injury site and organize to form a coherent structure at 9 dpci that persists throughout the regeneration process. Upon injury, endocardial cells strongly up-regulate the Notch pathway ligand delta like4 (dll4) and the Notch receptors notch1b, notch2 and notch3. Expression profiling showed that Notch signalling inhibition affects endocardial gene expression and genes related to extracellular matrix remodelling and inflammation. Gain- and loss-of-function experiments revealed that Notch is required for the organization of the endocardium, attenuation of the inflammatory response and cardiomyocyte proliferation. These results demonstrate a novel structural and signalling role for the endocardium during heart regeneration. Overall design: RNA was extracted from apical tip of heart ventricles 72h after cryoinjured adult zebrafish heart treated with DMSO (Controls) or RO gamma secretase inhibitor at 24 and 48h post injury.
Notch signalling restricts inflammation and <i>serpine1</i> expression in the dynamic endocardium of the regenerating zebrafish heart.
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View SamplesIn this study we analyzed the behavior of bone marrow MSC (BM-MSC) from MPN patients with the mutation in JAK2V617F. We initially characterized the biological function and gene expression profile changes in BM-MSC from MPN patients when compared to BM-MSC of healthy donors (HD). Then, we established co-cultures between MSC cell lines (HTERT and HS5) and the UKE-1 MPN cell line, and performed RT-PCR to study if the leukemic cells were able to modify the genes related to hematopoietic support.
Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis.
Specimen part, Disease stage, Subject
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