Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sex, Age, Specimen part
View SamplesCompare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Age, Specimen part
View SamplesTranscription is a major contributor to genome instability. A main cause of transcription-associated instability relies on the capacity of transcription to stall replication. Such genome instability is increased in RNAPII mutants.
RNA polymerase II contributes to preventing transcription-mediated replication fork stalls.
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Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sex, Age, Specimen part
View SamplesMultiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from 17 MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA. Taken together, these results showed that genomic heterogeneity, both at the DNA and RNA level, is a hallmark of MM transition from diagnosis to relapse.
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sex, 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.
No sample metadata fields
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.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Excess of Yra1 RNA-Binding Factor Causes Transcription-Dependent Genome Instability, Replication Impairment and Telomere Shortening.
No sample metadata fields
View SamplesThe conserved FACT (FAcilitates Chromatin Transcription) complex is a chromatin-reorganizing complex that promotes RNAPII transcription through chromatin templates by interacting with histones. It facilitates promoter activation by nucleosome eviction, and transcription elongation by nucleosome disruption and reassembly ahead and behind the RNAP. It also has a role in replication not fully understood yet. Genome-wide microarray analyses in spt16-11 and pob3-7 strains revealed a set of genes whose mRNA levels were altered with respect to the WT levels. These include 48 up-regulated and 80 down-regulated genes that are common to both strains. The up-regulated genes were longer and expressed at lower levels than the genome average whereas the down-regulated genes were more similar to the average of the genome.
The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts.
No sample metadata fields
View SamplesTranscription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with an imbalance proportion of Yra1, a component of THO/TREX.
Excess of Yra1 RNA-Binding Factor Causes Transcription-Dependent Genome Instability, Replication Impairment and Telomere Shortening.
No sample metadata fields
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