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 SamplesTranscriptome analysis of high-grade human ovarian adenocarcinomas. The hypothesis tested in the present study was that two reciprocal pathways, namely oxidative stress response and fibrosis, enable to build a hierarchical cluster of ovarian patients.
miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response.
Specimen part, Disease stage
View SamplesThis study was designed to provide additional insight into testicular hormone production and responsiveness in the orl strain and complement ongoing efforts to characterize the genetic basis of cryptorchidism in this isolated rat colony.
Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling.
Specimen part
View SamplesRNA-seq analysis of Drosophila pharate adults Overall design: Total RNA extracted from four lines of Drosophila melanogaster pharate adults were depleted of ribosomal RNAs and sequenced.
Vicinal: a method for the determination of ncRNA ends using chimeric reads from RNA-seq experiments.
Specimen part, Subject
View SamplesThe biotrophic fungus Ustilago maydis causes smut disease on maize (Zea mays L.), which is characterized by immense plant tumours. To establish disease and reprogram organ primordia to tumours, U. maydis deploys effector proteins in an organ-specific manner. However, the cellular contribution to leaf tumours remains unknown. We investigated leaf tumour formation on the tissue- and cell type-specific level. Cytology and metabolite analysis were deployed to understand the cellular basis for tumourigenesis. Laser-capture microdissection was performed to gain a cell-type specific transcriptome of U. maydis during tumour formation. In-vivo visualization of plant DNA synthesis identified bundle sheath cells as the origin of hyperplasic tumour cells, while mesophyll cells become hypertrophic tumour cells. Cell type specific transcriptome profiling of U. maydis revealed tailored expression of fungal effector genes. Moreover, U. maydis See1 was identified the first cell type specific fungal effector, being required for induction of cell cycle reactivation in bundle sheath cells. Identification of distinct cellular mechanisms in two different leave cell types, and See1 as an effector for induction of proliferation of bundle-sheath cells, are major steps in understanding U. maydis-induced tumor formation. Moreover, the cell-type specific U. maydis transcriptome data is a valuable resource to the scientific community. Overall design: To analyze the cell type specific transcriptome of U. maydis during the indcution of plant tumors, transcriptomic profiling of U. maydis from LCM-dissected tumour cells was done. At 4 dpi, SG200 infected HTT cells, bundle sheath-derived HPT cells, and SG200?see1 infected HTT cells (?see1 HTT) were isolated. As controls, mesophyll and bundle sheath cells from mock treated leaf tissue of the same age were isolated.
Cell type specific transcriptional reprogramming of maize leaves during Ustilago maydis induced tumor formation.
Specimen part, Subject
View SamplesThe chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4 mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS.
Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations.
No sample metadata fields
View SamplesFK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
Specimen part, Treatment
View SamplesSpheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the -catenin pathway. A parallel increase in the expression levels of -catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that -catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated -catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of -catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.
β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids.
Specimen part
View SamplesGene expression (by Affymetrix GeneChip Human 1.0ST) profiling of biopsy samples from recurrent, platinum resistant epithelial ovarian cancer patients before and after treatment of decitabine in combination with carboplatin. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in PBMC (14 paired samples), tumor (8 paired samples) and ascites (6 paired samples) (GSE31826).
Decitabine reactivated pathways in platinum resistant ovarian cancer.
Age
View SamplesThe mammalian telomere-binding protein Rap1 was found to have additional non-telomeric functions, acting as a transcriptional cofactor and a regulator of the NF-kB pathway. Here, we assess the effect of disrupting mouse Rap1 in vivo, and report on its unanticipated role in metabolic regulation and body weight homeostasis. Rap1 inhibition causes dysregulation in hepatic as well as adipose function. In addition, using a separation-of-function allele, we show that the metabolic function of Rap1 is independent of its recruitment to TTAGGG binding elements found at telomeres, and at other interstitial loci.
Nontelomeric role for Rap1 in regulating metabolism and protecting against obesity.
No sample metadata fields
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