O-GlcNAc Aminidase is an RNA Pol II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1b
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE86154 | GEO | 2016/08/29
SECONDARY ACCESSION(S): PRJNA340372
REPOSITORIES: GEO
Similar Datasets
Project description:We report the effect of splicing upon O-GlcNAc perturbation with OGT inhibitor or OGA inhibitor. We found that splicing is acutely affected through our phosphoproteomics data when cells are treated with OGT inhibitor. By obtaining the various splicing events that are affected by OGT or OGA inhibition, we found that O-GlcNAc is a major regulator of detained introns splicing. At early time point, we observed highly specific splicing of OGT/OGA detained introns to buffer O-GlcNAc changes. At longer time point, ~80% of the total detained introns are affected by O-GlcNAc perturbation, while the rest of canonical splicing events are only minimally affected (~ 5%).
2020-04-03 | GSE138783 | GEO
Project description:Single O-GlcNAc modification orchestrate by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA alias MGEA5) enzymes, affects signal transduction and gene expression by chromatin modulation. We developed Oga deleted MEF (mouse embryonic fibroblast) cells to investigate effects of O-GlcNAc modification in mice. RNA isolated from Mouse Embryonic Fibroblast cells generated from Oga Knock out (KO) Heterozygous (Het) and wild type (WT) cells and subjected to microarray analysis. Results provide insight into regulatory pattern of O-GlcNAc modification, and associated signaling pathways
2014-12-29 | GSE52721 | GEO
Project description:The addition of O-GlcNAc (a single β-D-N-acetylglucosamine sugar at serine and threonine residues) by O-GlcNAc transferase (OGT) and removal by O-GlcNAcase (OGA) maintains homeostatic levels of O-GlcNAc. We investigated the role of OGlcNAc homeostasis in hematopoiesis utilizing G1E-ER4 cells carrying a GATA-1 transcription factor fused to the estrogen receptor (GATA-1ER) that undergo erythropoiesis following the addition of β-estradiol (E2) and myeloid leukemia cells that differentiate into neutrophils in the presence of all-trans retinoic acid. During G1E-ER4 differentiation, a decrease in overall O-GlcNAc levels and an increase in GATA-1 interactions with OGT and OGA were observed. Transcriptome analysis on G1E-ER4 cells differentiated in the presence of Thiamet-G (TMG), an OGA inhibitor, identified expression changes in 433 GATA-1 target genes. Chromatin immunoprecipitation demonstrated that the occupancy of GATA-1, OGT, and OGA at Laptm5 gene GATA site was decreased with TMG. Myeloid leukemia cells showed a decline in O-GlcNAc levels during differentiation and TMG reduced the expression of genes involved in differentiation. Sustained treatment with TMG in G1E-ER4 cells prior to differentiation caused a reduction of hemoglobin positive cells during differentiation. Our results show that alterations in O-GlcNAc homeostasis disrupt transcriptional programs causing differentiation errors suggesting a vital role of O-GlcNAcylation in control of cell fate.
2018-11-06 | GSE122104 | GEO
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:O-linked N-acetylglucosamine (O-GlcNAc) is a necessary protein modification installed onto hundreds of nucleocytoplasmic proteins by O-GlcNAc transferase (OGT). Recently, we developed an antibody-free metabolic feeding approach that enables unbiased mapping of O-GlcNAcylated proteins in a genome-wide manner, providing insight into the regulation of genes by O-GlcNAcylated proteins within Drosophila. Here we apply this O-GlcNAc chemical mapping strategy to a time course (TC) feeding experiment within Drosophila larvae, generated the first ever TC ChIP-seq experiment performed on both a protein modification and within a living organism. TC metabolic labeling experiments were performed in wild-type and O-GlcNAc hydrolase (OGA) deficient Drosophila. Analysis of the resulting sequencing data revealed that a loss of OGA causes a global increase in the retention of O-GlcNAc modification on proteins bound to the genome, suggesting most nuclear proteins are sensitive to effects of O-GlcNAc cycling. Interestingly, some loci are more sensitive to the impacts of a loss of OGA compared to others. This study will present an improved understanding of the regulation of gene expression by O-GlcNAc while providing the broader community with experimental methods for time-resolved analysis of genome-wide binding by proteins.
2020-01-07 | GSE124785 | GEO
Project description:We performed RNA sequencing on HeLa cells treated with OGT inhibitor (Ac4-5SGlcNAc), DMSO, or OGA inhibitor (Thiamet-G) and obtained about 100 million paired-end reads (150 bp) for each replicate. Then the sequencing data was analyzed by MISO to select the O-GlcNAc-regulated alternative splicing events.
2019-05-13 | GSE131067 | GEO
Project description:Drosophila development is a complex and dynamic process regulated, in part, by members of the Polycomb (Pc), Trithorax (Trx) and Compass chromatin modifier complexes. O-GlcNAc Transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. OGT transfers N-acetyl-D-glucosamine (GlcNAc) onto hydroxyl groups of serine or threonine residues of key transcriptional regulators using the nutrient-derived UDP-GlcNAc as a substrate, which is dynamically removed by O-GlcNAcase (OGA). We performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in Drosophila S2 cells and found that O-GlcNAc was elevated genome wide particularly at genes related to mitosis and cell cycle in OGA RNAi cells, but not at sites co-occupied by Pc member Pleiohomeotic (Pho), such as the Hox and NK homeobox gene clusters. Microarray analysis suggested that altered O-GlcNAc cycling perturbed the expression of genes associated with morphogenesis and cell cycle regulation. To examine the in vivo consequences of disturbed O-GlcNAc cycling in the whole animal, we produced a null allele of oga (ogadel.1) in Drosophila. Epigenetic activators including Trx group members Trithorax (Trx), Absent small or homeotic discs 1 (Ash1) and Compass member Set1 histone methyltransferases are O-GlcNAc modified in ogadel.1 mutants. ogadel.1 mutants displayed altered expression of a distinct set of cell cycle related genes in ovaries. Our results suggest that the loss of OGA could affect epigenetic machinery by accumulating O-GlcNAc on numerous chromatin factors including Trx, Ash1 and Set1 in Drosophila. We performed affymetrix tilingarray analysis after OGT or OGA RNAi knockdown in Drosophila S2 cells to find if that O-GlcNAc was elevated genome wide particularly at genes related to mitosis and cell cycle in OGA RNAi cells, but not at sites co-occupied by Pc member Pleiohomeotic (Pho), ------------------------------- This represents the gene expression component only
2016-07-21 | E-GEOD-74846 | biostudies-arrayexpress
Project description:An X-chromosome exome sequencing analysis identified a mutation in O-GlcNAc transferase (OGT) (pL254F) in a family with X-linked intellectual disability (XLID). Affected patient lymohoblastoids exhibit decreased steady state OGT levels owing to an unstable protein compared to the unaffected, related male controls. Suprisingly, global O-GlcNAc levels remained remained unaltered. This prompted us to check the both protein and mRNA levels of the other cycling enzyme, O-GlcNAcase (OGA) which was also lowered. This implies that a compensation mechanism exists, however imperfect, owing to the disease state of the individuals. We performed glabal transcriptome analysis to assess any other changes in message between patients and controls. Our study highlights small differences in the global transcriptome of patient lymhoblastoids that have the L254F mutation in O-GlcNAc transferase when compared to familial controls using Illumina sequencing of total RNA
2016-02-25 | E-GEOD-74263 | biostudies-arrayexpress
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:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. In C. elegans, three mutant strains(genotypes used: N2 (wild-type), ogt-1 (ok1474), oga-1 (ok1207), and pmk-1 (km25)) were treated with the human pathogen S. aureus (SA) or P. aeruginosa(PA) and OP50 (E. coli control) with three biological replications.
2015-05-01 | E-GEOD-53732 | biostudies-arrayexpress