MiR-31 is one of the most highly overexpressed miRNAs in psoriasis skin; however, its biological role in the disease has not been studied. Here we show that miR-31 is markedly overexpressed in psoriasis keratinocytes. To study the biological role of miR-31 in keratinocytes, we transfected miR-31 hairpin inhibitor (anti-miR-31) into primary human keratinocytes to inhibit endogenous miR-31. We performed a global transcriptome analysis of keratinocytes upon suppression of endogenous miR-31 using Affymetrix arrays.
MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40.
Specimen part
View SamplesPolycomb group (PcG) proteins bind to and repress genes in embryonic stem cells and through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark, H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminal differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing the dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinsons disease. Overall design: 12 mice were used for RNAseq, 4 conditions, 3 mice per condition.
Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism.
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View SamplesFNDC4 is a novel secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in various mouse models of inflammation as well as in human inflammatory conditions. Specifically, subjects with inflammatory bowel disease show increased FNDC4 levels locally at inflamed sites of the intestine. Interestingly, administration of recombinant FNDC4 during colitis development in mice resulted in markedly reduced disease severity compared to mice injected with a control protein. Conversely, mice that lacked Fndc4 showed increased colitis severity. Analysis of binding of FNDC4 to different immune cell types revealed strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro resulted in reduced phagocytosis, improved survival and reduced pro-inflammatory chemokine expression. Hence, treatment with FNDC4 resulted in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized a novel factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.
FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Digital gene expression profiling of primary acute lymphoblastic leukemia cells.
Specimen part, Disease, Disease stage
View SamplesThe aim of this study was to benchmark digital gene expression (DGE) profiling by massively parallel sequencing against the most commonly used method for gene expression analysis. We compared the DGE levels to expression levels from Affymetrix arrays. Data from Affymetrix Human Genome U133 plus 2.0 GeneChips was available for 12 of the 21 RNA samples from ALL patient cells analyzed by DGE.
Digital gene expression profiling of primary acute lymphoblastic leukemia cells.
Specimen part, Disease, Disease stage
View SamplesThe influenza A(H1N1)pdm09 virus caused a global flu pandemic in 2009 and contributes to seasonal epidemics. Different treatment and prevention options for influenza have been developed and applied with limited success. Here we report that an Akt inhibitor MK2206 possesses potent antiviral activity against influenza A(H1N1)pdm09 virus in vitro. We showed that MK2206 blocks the entry of different A(H1N1)pdm09 strains into cells. Moreover, MK2206 prevented A(H1N1)pdm09-mediated activation of cellular signaling pathways and the development of cellular immune responses. Importantly, A(H1N1)pdm09 virus was unable to develop resistance to MK2206. Thus, MK2206 is a potent anti-influenza A(H1N1)pdm09 agent.
Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia.
Specimen part, Disease, Disease stage
View SamplesWe surveyed the genome-wide DNA methylation levels and gene expression patterns in patients with pediatric acute lymphoblastic leukemia. Using Affymetrix U133 Plus 2.0 GeneChips, we identified a relatively small set of CpG sites that are highly correlated with gene expression.
Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset.
Sex, Specimen part, Cell line
View SamplesThe MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif Ohler 5. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex.
The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset.
Cell line
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