O-GlcNAc sites identification on SDHA
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Weijie Qin
PROVIDER: PXD078261 | iProX | Wed May 13 00:00:00 GMT+01:00 2026
REPOSITORIES: iProX
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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: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:O-GlcNAcylation is the modification of serine and threonine residues with beta-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. To investigate the role of protein O-GlcNAcylation on intestinal homeostasis, we generated intestinal epithelial cell (IEC)-specific O-GlcNAc transferase (OGT) knockout in mice. The KO mice developed spontanous intestinal inflammation. To determine the underlying molecular mechanisms, we performed RNA sequencing of ileum and colon epithelial cells of wildtype and IEC-OGT KO mice.
2017-06-27 | GSE100473 | GEO
Project description:Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Acting in multimeric protein complexes, these factors control structure and function of chromatin. We used a robust affinity purification mass spectrometry (AP-MS) approach to systematically map the PcG protein interactome in a single human cell line. Importantly, we uncovered the topology map of the human PR-DUB de-ubiquitination complexes, which comprise the O-linked N-acetylglucosamine transferase OGT1 and a number of transcription factors. Here we provide genome-wide chromatin maps of identified PR-DUB1 subunits ASXL1, FOXK1 and the OGT1 catalyzed modification O-GlcNAc based on ChIP-seq. Our data set comprises 3 ChIP-seq samples plus 2 input control samples using chromatin from Flp-In HEK293 T-REx cells cells which was immunoprecipitated using antibodies against ASXL1, FOXK1 and O-GlcNAc.
2016-09-08 | E-GEOD-51673 | 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:The Arabidopsis thaliana glycosyl transferases SPINDLY (SPY) and SECRET AGENT (SEC) modify nuclear and cytosolic proteins with O-linked fucose or O-linked Nacetylglucosamine (O-GlcNAc), respectively. O-fucose and O-GlcNAc modifications can occur at the same sites. SPY interacts physically and genetically with GIGANTEA (GI), suggesting that it could be modified by both enzymes. Previously, we found that, when co-expressed in Escherichia coli, SEC modifies GI; however, the modification site was not determined. By analyzing the overlapping sub-fragments of GI, we identified a region that was modified by SEC in E. coli. Modification was undetectable when threonine 829 (T829) was mutated to alanine, while the T834A and T837A mutations reduced the modification, suggesting that T829 was the primary or the only modification site. Mapping using mass spectrometry detected only the modification of T829. Previous studies have shown that the positions modified by SEC in E. coli are modified in planta, suggesting that T829 is O-GlcNAc modified in planta.
2024-07-15 | PXD053909 | Pride
Project description:Chromatin modifier metastatic tumor protein 1 (MTA1), closely correlated with the development and progression in breast cancer, has a fantastic role in multiple cellular processes, including gene expression and cell homeostasis. Although MTA1 is a stress-responsive gene, its role in genotoxic adaptation remains unexplored. Here, we demonstrate that O-GlcNAc modification promotes MTA1 to interact with chromatin and regulates target gene expression, contributing to breast cancer cell genotoxic adaptation. MTA1 is modified with O-GlcNAc residues at serine 237/241/246 in adriamycin adaptive breast cancer cells and that modification improves the genome-wide interactions of MTA1 with gene promotor regions by enhancing its association with nucleosome remodeling and histone deacetylation (NuRD) complex. Further, O-GlcNAc-modulated MTA1 chromatin-binding influences the specific transcriptional regulation of genes involved in the adaptation of breast cancer cells to genotoxic stress. We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-HA magnetic beads in HA-MTA1-WT or HA-MTA1-3A stably expressed MCF-7 cells. Next-generation sequencing libraries were generated and amplified for 15 cycles with BGISEQ kit. 100-300 bp DNA fragments were gel-purified and sequenced with BGISEQ-500 (BGI). Two biological replicates of the ChIP-seq were performed. We also analyzed gene expression in MTA1-WT and MTA1-3A expressed cells by RNA-seq.
2020-12-10 | GSE162932 | GEO
Project description:Prolonged exposure to antigens drives CD8+ cytotoxic T lymphocytes (CTLs) to a hypofunctional state known as exhaustion, which compromises their ability to control infections and cancer. Here, we identify O-GlcNAcylation (O-GlcNAc)—a nutrient-sensitive post-translational modification—as a critical regulator for CTL exhaustion. Exhausted CTLs elevated nucleus O-GlcNAc levels, coupled with increased levels of the cellular uridine diphosphate GlcNAc (UDP-GlcNAc) relative to their effector counterparts. Using quantitative chemoenzymatic O-GlcNAcomic analysis, we identified a T-box transcription factor downstream of TCF-1-centered exhaustion transition and sustenance, eomesodermin (Eomes), which undergoes intensive O-GlcNAcylation. Mechanistically, mutation of the primary O-GlcNAc sites on Eomes abolished its glycosylation, but their phosphorylation and interactions with O-GlcNAc transferase (OGT) were unaffected. OGT/Eomes was indispensable for interaction with TCF-1. OGT stabilized Eomes and increased its accumulation in the nucleus, where T-bet-to-Eomes transcriptional transition drives functional exhaustion. These results uncover a novel regulatory relationship between OGT and the TCF-1/Eomes axis in promoting CTL exhaustion and impairing their protective function.
2025-07-01 | GSE298788 | 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:The modification of intracellular proteins by monosaccharides of O-linked linked β-N-acetylglucosamine (O-GlcNAc) is thought to mediate proteins by regulating protein phosphorylation, either by modifying and modulating protein kinases or by competing with phosphorylation for hydroxyl residues. To provide molecular insight into the pathways regulated by O-GlcNAc that promote survival in basal conditions or during cellular stress, we have utilized SILAC-based quantitative proteomics to carry out comparisons of site-specific phosphorylation in OGT wild-type (WT) and Null cells. Quantitation of the phosphoproteome demonstrated that out of 5,529 serine/threonine/tyrosine phosphorylated sites, 231 phosphosites were upregulated and 133 downregulated in the absence of O-GlcNAc. The data identified widespread changes in the phosphoproteome upon removal of O-GlcNAc, suggesting that O-GlcNAc regulates processes such as the cell cycle, genomic stability, inflammatory responses and lysosomal biogenesis.
2015-01-28 | PXD001153 | Pride