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GSE48463
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signalling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating haematopoietic cells, was studied in non-induced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed an enrichment of mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor activated kinase-1 (TAK1), a central player in TLR4 signalling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis and stability, but enhances TAK1 mRNA translation, resulting in elevated TNF-alpha, IL-1beta and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in non-induced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesised TAK1 initiates the inflammatory response of macrophages.
Publication Title
Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Protein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Publication Title
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 159 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice.
Publication Title
Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, F508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-F508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
Publication Title
A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Sus scrofa
- 121 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 73 Downloadable Samples
IlluminaHiSeq2500
Description
CSL is a key transcription factor, mostly acting as a repressor. While known as main effector of Notch signaling, it can also play Notch-independent functions. Despite the wide interest in CSL, the mechanisms responsible for its own regulation have been little studied. We recently showed that CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts, which promote keratinocyte tumor development. We show here that levels of CSL gene transcription differ among HDF strains derived from many different individuals, with negative correlation with genes involved in DNA damage/repair. CSL expression in all tested strains is negatively regulated by stress / DNA damaging insults caused by UVA, Reactive Oxygen Species (ROS), smoke extract and doxorubicin treatment. p53, a key effector of the DNA damage response, functions as common negative regulator of CSL gene transcription, through both suppression of CSL promoter activity and, indirectly, through increased p21 expression. CSL was previously shown to bind p53 suppressing its activity. The present findings indicate that p53, in turn, decreases CSL expression, which can serve to enhance p53 activity in the acute response of cells to DNA damaging cancer-threatening conditions. Overall design: RNA sequencing of 46 human foreskin fibroblasts
Publication Title
Negative control of CSL gene transcription by stress/DNA damage response and p53.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 67 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 62 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 59 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn).
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 24 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples