Phosphorylation of histone H3 at Serine 10 emerges as a mechanism increasing chromatin accessibility of the transcription factor NF-kB for a particular set of immune genes. Here we report that a bacterial pathogen uses this strategy to shape the transcriptional response of infected host cells. We identify the Shigella flexneri type III protein effector OspF as a Dual Specific Phosphatase. OspF dephosphorylates MAP kinases within the nucleus impairing histone H3 phosphorylation at Serine 10 in a gene-specific manner. Therefore, OspF reprograms the transcriptional response for inactivation of a subset of NF-kB responsive genes. This regulation leads to repression of polymorphonuclear leukocytes recruitment in infected tissues. Thus, pathogens have evolved the ability to precisely modulate host cell epigenetic information as a strategy to repress innate immunity.
An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.
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View SamplesWe have here followed the transcriptional effect of stimulation with the phorbol ester PMA in mouse fibroblasts from HP1gamma null mice recomplemented with either wild-type HP1gamma or an HP1g with an S83A mutation Overall design: Spontaneously immortalized mouse embryonic fibroblasts from HP1gamma null mice were used to stably integrate either an empty expression vector, or expression vectors for either WT or S83A mutant HP1gamma. These cells were then stimulated with PMA for 0 or 60 min. and used for transcriptome analysis by Next Generation sequencing.
Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF.
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View SamplesA total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR < 0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR < 0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated.
A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
Disease, Disease stage
View SamplesWhen compared to skin, oral mucosal wounds heal rapidly and with reduced scar formation. This study used an Affymetrix microarray platform to compare the transcriptomes of oral mucosa and skin wounds in order to identify critical differences in the healing response at these two sites.
Positional differences in the wound transcriptome of skin and oral mucosa.
Sex, Specimen part
View Samplesanalyzed changes in cytokine/chemokine production and gene expression levels in, human peripheral blood mononuclear cells upon teratment with 15M,2,4-benzenetriol
Identification of human cell responses to benzene and benzene metabolites.
No sample metadata fields
View SamplesKaposis sarcoma (KS) is the most frequently occurring malignant tumor in patients infected with the human immunodeficiency virus. Recent studies have revealed that infection of vascular endothelial cells with Kaposi's sarcoma-associated herpes virus in vitro results in a lymphatic re-programming of these cells, with potent induction of the lymphatic marker genes podoplanin and VEGFR-3 which is mediated by upregulation of the transcription factor Prox1. However, the potential effects of Prox1 expression on the biology of KS and, in particular, on the aggressive and invasive behavior of KS tumors in vivo have remained unknown. We stably expressed Prox1 cDNA in the two mouse hemangioendothelioma cell lines EOMA and Py-4-1, well-established murine models for kaposiform hemangioendothelioma. Surprisingly, we found that expression of Prox1 was sufficient to induce a more aggressive behavior of tumors growing in syngenic mice, leading to enhanced local invasion into the muscular layer and to cellular anaplasia. This enhanced malignant phenotype was associated with upregulation of several genes involved in proteolysis, cytoskeletal reorganisation and migration. Together, these results indicate that Prox1 plays an important, previously unanticipated role in mediating the aggressive behavior of vascular neoplasms such as Kaposi's sarcoma.
Prox-1 promotes invasion of kaposiform hemangioendotheliomas.
No sample metadata fields
View SamplesHere, using genome wide analysis, we demonstrate that canonical mRNA is processed post-transcriptionally through an alternative cleavage and polyadenylation mechanism. As a result of this process, the downstream cleavage fragment of the 3'UTR remains uncapped and stable This finding indicates that different parts of gene mRNA are separate and independent, by re-annotating the human transcriptome using this model, we provide a new overview of the function and impact of microRNA (miRNA) Our results shed new light on the mammalian transcriptome and show that what were considered as 3'UTRs are in fact autonomous RNA fragments. Overall design: Examination of mRNA levels and cleavage across transcripts in U2OS and 293 cell types (3 replicates each)
Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments.
Treatment, Subject
View SamplesRNA-seq experiment on five mouse brain regions-- --comparing expression in virgin females to primiparous females three weeks after pup weaning. For each brain region there are 8 replicates, though three samples were not used in the final analysis based on inspection of PCA plots (1 sample from the Hippocampus, Cerebellum and Amygdala data sets; see details below). Overall design: Comparison of gene expression in five brain regions between eight virgin and eight primiparous females three weeks after pup weaning. Pair-wise comparisons were performed using EdgeR transformed data and Limma Voom for statistical analysis.
Maternal Experience Leads to Lasting Gene Expression Changes in Some Regions of the Mouse Brain.
Specimen part, Cell line, Subject
View SamplesTo investigate whether and how expression of the oncogenic transcription factor EVI1 influences gene regulation by phorbol esters and vice versa, the human myeloid cell line U937 was transduced with an EVI1 expression vector or empty vector as a control. Cells were treated with 12-Otetradecanoylphorbol 13-acetate (TPA) or its solvent ethanol as a control. RNA was extracted and subjected to gene expression microarray analysis.
The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.
Cell line
View SamplesThe product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-b superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects.
The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid.
Cell line
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