Dynamic O-GlcNAc cycling at promoters of C. elegans genes regulating Longevity, Stress, and Immunity
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE18132
PROVIDER: PRJNA119415 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: Not available
| S-EPMC2867743 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2010-01-01 | GSE18132 | GEO
Project description:Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. Knockouts of the O-GlcNAc cycling enzymes in C. elegans are viable and fertile, allowing a global analysis of the impact of GlcNAcylation. Whole genome ChIP profiling of the O-GlcNAc cycling mutants identified over 800 genes associated with GlcNAcylated chromatin. This novel chromatin mark is preferentially found with genes involved in stress, longevity, and innate immunity, the same set of processes affected by global changes in gene expression analysis. This experiment collected data on fed animals (3 hours) for comparisons to previoulsy collected starved data to see what acute effects nutritional flux would have on either O-GlcNAc chromatin marks or RNA Pol II distributions.
2010-01-01 | GSE18611 | GEO
Project description:The reversible posttranslational O-GlcNAc modification of serine or threonine residues of intracellular proteins is involved in many cellular events from signaling cascades to epigenetic and transcriptional regulation. O-GlcNAcylation is a conserved nutrient-dependent process involving two enzymes, O-GlcNAc Transferase (OGT) adding O-GlcNAc while O-GlcNAcase (OGA) removing it in a manner that’s protein and context dependent. O-GlcNAcylation is essential for epigenetic regulation of gene expression through its action on Polycomb and Trithorax and Compass complexes. However, the important role of O-GlcNAc on adult life and healthspan have been largely unexplored, mainly due the lack of available model systems. Cataloging the O-GlcNAc proteome has proven useful in understanding the biology of this modification in vivo. In this study, we leveraged a recently developed oga knockout fly mutant to identify the O-GlcNAcylated proteins in adult Drosophila melanogaster. The adult O-GlcNAc proteome revealed many proteins related to cell and organismal growth, development, differentiation, and epigenetics. We identified many O-GlcNAcylated proteins that serve a role in increased growth and decreased longevity, including HCF, SIN3A, LOLA, KISMET, ATX2, SHOT, and FOXO.
2021-04-26 | PXD025344 | Pride
Project description:Heparan sulfate (HS), a long linear polysaccharide, is implicated in various steps of tumorigenesis, including angiogenesis. We successfully interfered with HS biosynthesis using a peracetylated 4-deoxy analog of the HS constituent GlcNAc and studied the compoundM-bM-^@M-^Ys metabolic fate and its effect on angiogenesis. The 4-deoxy analog was activated intracellularly into UDP-4-deoxy-GlcNAc and HS expression was inhibited up to ~96% (IC50 = 16 M-BM-5M). HS chain size was reduced, without detectable incorporation of the 4-deoxy analog, likely due to reduced levels of UDP-GlcNAc and/or inhibition of glycosyltransferase activity. Comprehensive gene expression analysis revealed reduced expression of genes regulated by HS binding growth factors as FGF-2 and VEGF. Cellular binding and signaling of these angiogenic factors was inhibited. Micro-injection in zebrafish embryos strongly reduced HS biosynthesis, and angiogenesis was inhibited in both zebrafish and chicken model systems. All these data identify 4-deoxy-GlcNAc as a potent inhibitor of HS synthesis which hampers pro-angiogenic signaling and neo-vessel formation. 9 samples were analyzed: 3 biological replicates from untreated SKOV3 cells, 3 biological replicates from SKOV3 cells treated with peracetylated GlcNAc, 3 biological replicates from SKOV3 cells treated with peracetylated 4-deoxy-GlcNAc
2013-08-23 | E-GEOD-48284 | biostudies-arrayexpress
Project description:Dysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with β-linked N-acetylglucosamine (O- glcnAcylation) via overexpression of the O-glcnAc–regulating enzymes O- glcnAc transferase (OGT) or O- glcnAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O- glcnAcylation either by pharmacological or genetic manipulation also alters metabolic function. Sustained O-glcnAc elevation in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular respiration and ROS generation. Cells with elevated O-glcnAc levels had elongated mitochondria and increased mitochondrial membrane potential, and RNA-Seq in SH-SY5Y cells indicated transcriptome reprogramming and down regulation of the NRF2-mediated antioxidant response. Sustained O-glcnAcylation in mice brain and liver validated the metabolic phenotypes observed in the cells, and OGT knockdown in the liver elevated ROS levels, impaired respiration, and increased the NRF2 antioxidant response. Moreover, elevated O-glcnAc levels promoted weight loss and lowered respiration in mice and skewed the mice toward carbohydrate-dependent metabolism as determined by indirect calorimetry. In summary, sustained elevation in O-glcnAcylation coupled with increased OGA expression reprograms energy metabolism, a finding that has potential implications for the etiology, development, and management of metabolic diseases.
2017-07-20 | GSE101642 | GEO
Project description:Tissue fibrosis is induced by chronic inflammation accompanied by repeated injuries. Chronic inflammation alters fibroblasts and stellate cells, maintaining the tissues in myofibroblasts and activating stellate cells. This activation promotes the augmentation of these cells and the abundant production of extracellular matrices, such as collagen. Fibrotic tissue dysfunction is eventually induced by expelling parenchymal cells with these abundant collagen depositions. To recover from tissue fibrosis, the activation of myofibroblasts and stellate cells is suppressed by selectively targeting these cells. Here we show that O-N-acetylglucosamine (GlcNAc)-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the GlcNAc moiety of these proteins suppress the activation of these cells; administration of the GlcNAc-bearing polymer into carbon tetrachloride-treated mice can improve liver fibrosis. We found that a multivalent GlcNAc moiety structure elicited antifibrotic activities in myofibroblasts by interacting with cell surface vimentin and desmin. Therefore, since these cells highly express cytoskeletal proteins, vimentin and desmin, on the cell surface and have GlcNAc-binding activity, we suggest that O-GlcNAc-modified proteins leaked from dead cells can function as suppressors of fibrosis and hyperplasia in spontaneous recovery. Moreover, we anticipate that GlcNAc-bearing polymers mimicked by O-GlcNAc-modified proteins will be useful as new therapeutic tools for fibrosis and hyperplasia.
2022-03-30 | GSE199656 | GEO
Project description:ChIP-seq shows that OGA and O-GlcNAc are found at promoters/TSS concomitantly with the known elongation factors SPT5 and TIF1b as well as RNA pol II. There are gene body overlaps of various combinations of factors as well.
2016-08-29 | GSE86154 | GEO
Project description:We report that Oct4 is modified by O-GlcNAc in stem cells. To find O-GlcNAc-Oct4 target genes, we ChIPed Oct4 with Flag(Oct4) antibody and then O-GlcNAc modified proteins are enriched by sWGA beads (succinylated wheat germ agglutinin (sWGA), which specifically binds O-GlcNAc). Results show that several genes implicated in pluripotency regulation are bound by O-GlcNAc-Oct4 in their gene region. 2 samples examined: Control (ChIP with anti-Flag(Oct4) and then reChIP with IgG), O-GlcNAc-Oct4 (ChIP with anti-Flag (Oct4) and then reChIP with sWGA)
2012-08-27 | E-GEOD-36388 | biostudies-arrayexpress
Project description:Beauveria bassiana is a popular and eco-friendly biopesticide. Sensing N-acetylglucosamine (GlcNAc) , a building block of both insect exoskeleton and fungal cell wall, might play a vital role during B. bassiana pathogen-pest interaction. Previous studies in Candida albicans have demonstrated that a GlcNAc sensor (termed as Ngs1) was in response to GlcNAc signal sensing and transportation. Herein, we found a Ngs1 homology in B. bassiana, and reported the alteration of transcriptomic profiles between wild-type strain and Ngs1-deletion mutants grown on cuticle broth (CB) supplemented with 1% cuticle powder of Locusta migratoria exoskeleton, followed by shaking at 150 rpm for 5 days at 25 ℃.
2024-05-31 | GSE267338 | GEO