Neurons exploit mRNA localization and local translation to spatio-temporally regulate gene expression during development. Local translation and retrograde transport of transcription factors regulate nuclear gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuronal-like cells and of hippocampal neurons. We show that Hmgn5 3UTR drives growth cone localization and translation of a reporter gene, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth while HMGN5 overexpression induces neurite outgrowth and global chromatin decompaction. Interestingly, control of both neurite outgrowth and chromatin structure is dependent on proper growth cone localization of Hmgn5 mRNA. Our results provide the first evidence that mRNA localization and local translation might serve as a mechanism to couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.
Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth.
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View SamplesMouse embryonic fibroblasts deficient for p53 and expressing mutant RasV12 were infected with lentiviral constructs carrying short hairpin RNAs targeting ARF or a scrambled control. Four days post infection, cells were harvested for microarray analysis.
ARF and p53 coordinate tumor suppression of an oncogenic IFN-β-STAT1-ISG15 signaling axis.
No sample metadata fields
View SamplesWe compared gene expression profiles of a human CD4+ T-cell line 24 h after infection with a cell line of the same origin permanently releasing SIVmac251/32H. A new knowledge-based-network approach (Inter-Chain-Finder) was used to identify subnetworks leading to resistance to SIV-induced cell death. Notably, the method can identify not only differentially-expressed key hub genes but also non-differentially expressed, critical, hidden regulators.
Identification of molecular sub-networks associated with cell survival in a chronically SIVmac-infected human CD4+ T cell line.
Disease, Disease stage
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Fingolimod alters the transcriptome profile of circulating CD4+ cells in multiple sclerosis.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Fingolimod alters the transcriptome profile of circulating CD4+ cells in multiple sclerosis.
Sex, Subject
View SamplesThe transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 8 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated that the suppression of Keap1 expression induced genes that are involved in anti-oxidative stress defense and biotransformation, pathways proving the activation of Nrf2 by the siRNAs against Keap1. The expression of neither fatty acid- nor carbohydrate-handling proteins was regulated by the suppression of Keap1. Metabolic profiling of the animals did also not show effects on plasma and hepatic lipids, energy expenditure or glucose tolerance by the activation of Nrf2. The data indicate that hepatic Nrf2 is not a major regulator of intermediary metabolism in mice.
Chronic Activation of Hepatic Nrf2 Has No Major Effect on Fatty Acid and Glucose Metabolism in Adult Mice.
Specimen part, Treatment
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
High-Resolution Expression Profiling of Peripheral Blood CD8<sup>+</sup> Cells in Patients with Multiple Sclerosis Displays Fingolimod-Induced Immune Cell Redistribution.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
High-Resolution Expression Profiling of Peripheral Blood CD8<sup>+</sup> Cells in Patients with Multiple Sclerosis Displays Fingolimod-Induced Immune Cell Redistribution.
Sex, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View Samples