Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion
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ABSTRACT:
PROVIDER: PRJNA796947 | ENA |
REPOSITORIES: ENA
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Project description:The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes. Though sustained hyper-O-GlcNAcylation aggravates pathogenesis of many chronic diseases, accumulating evidence also indicates that acute augmentation in O-GlcNAcylation seems to benefit disease healing in some cases. Glucosamine (GlcN) is a freely available and commonly used dietary supplement for human cartilage health, which also activates the hexosamine biosynthesis pathway and induces protein O-GlcNAcylation. Here we show that both GlcN early and late therapies effectively facilitate cardiac recovery in mice by elevating accumulation of Ly6Clow Mo/Mps in infarcted hearts. Eliminating Mo/Mps with clodronate liposomes fully abolishes aforementioned cardiac healing role of GlcN. Importantly, GlcN supplementation accelerates not only in vitro mobility of reparative Mo/Mps but also in vivo infiltration of Ly6Clow Mos. Mechanistically, GlcN positively regulates transcription of myeloid CX3C chemokine receptor 1 (Cx3cr1) by improving STAT1 O-GlcNAcylation, which stabilizes STAT1 and subsequently promotes chemotaxis and infiltration of Ly6Clow Mos. In summary, we identify a novel anti-inflammatory role of GlcN and suggest that its protective effects are mediated through chemotaxis of Ly6Clow Mos in a STAT1/CX3CR1-dependent fashion, which is controlled by O-GlcNAcylation of STAT1. Our study provides a novel clue for Mo/Mps modulator therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.
2022-04-06 | GSE193613 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE33049: GlcNAcylation of histone H2B facilitates its monoubiquitination [Illumina Genome Analyzer data] GSE33050: GlcNAcylation of histone H2B facilitates its monoubiquitination [Affymetrix data] Refer to individual Series
2011-10-26 | E-GEOD-33051 | biostudies-arrayexpress
Project description:We report that histone GlcNAcylation of H2B S112 is a vital histone modification which facilitates histone monoubiquitination (ub). In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over entire chromosomes including transcribed gene loci, together with co-localization of H2B S112 GlcNAcylation and K120 ub. Examination of H2B S112 GlcNAc and H2B K120 ub in HeLa S3 cells
2011-10-27 | E-GEOD-33049 | biostudies-arrayexpress
Project description:Ligand-stimulated epidermal growth factor receptor (EGFR) signaling plays fundamental roles in normal cell physiology, such as cell growth, cell proliferation, and cell survival. Deregulation of EGFR signaling contributes to the development and progression of diseases including cancer. Despite its essential role in biology, the mechanisms by which EGFR signaling is regulated in cells are still poorly understood. Here, we demonstrate that O-linked N-acetyl-glucosamine (O-GlcNAc) modification serves as an important regulator of EGFR intracellular trafficking and degradation. Mechanistically, O-GlcNAcylation of hepatocyte growth factor regulated tyrosine kinase substrate (HGS), a key protein in EGFR intraluminal sorting pathway, inhibits HGS interaction with signal-transducing adaptor molecule (STAM), thereby impairing the formation of endosomal sorting complex required for transport-0 (ESCRT-0). Moreover, O-GlcNAcylation increases HGS ubiquitination and decreases its protein stability in cells. Consequently, HGS O-GlcNAcylation inhibits EGFR intraluminal sorting and lysosomal degradation, leading to the accumulation of EGFR and prolonged EGFR signaling in cells.
2022-04-04 | PXD031700 | Pride
Project description:We report that histone GlcNAcylation of H2B S112 is a vital histone modification which facilitates histone monoubiquitination (ub). In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over entire chromosomes including transcribed gene loci, together with co-localization of H2B S112 GlcNAcylation and K120 ub.
2011-10-27 | GSE33049 | GEO
Project description:Pancreatic Gene Expression from Wild-Type, Stat1-Transgenic, and Stat1-CC-Transgenic Mice. This data was part of the set of data utilized to identify PARP9/DTX3L as a novel antiviral gene. Keywords: transgene state analysis RNA was extracted from the pancreas of 3 mice per genotype (wild-type, Stat1-Transgenic, Stat1-CC-Transgenic). Comparisons were made between Stat1-Transgenic and Stat1-CC-Transgenic mice.
2015-09-01 | E-GEOD-61414 | biostudies-arrayexpress
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:O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this knowledge gap, we investigated the global transcriptional response to perturbations in O-GlcNAcylation. Unexpectedly, many transcriptional effects of O-GlcNAc transferase (OGT) inhibition were due to the activation of NRF2, the master regulator of redox stress tolerance. Moreover, we found that a signature of low OGT activity strongly correlates with NRF2 activation in multiple tumor expression datasets. Guided by this information, we identified KEAP1 (also known as KLHL19), the primary negative regulator of NRF2, as a direct substrate of OGT. We show that O-GlcNAcylation of KEAP1 at serine 104 is required for the efficient ubiquitination and degradation of NRF2. Interestingly, O-GlcNAc levels and NRF2 activation co-vary in response to glucose fluctuations, indicating that KEAP1 O-GlcNAcylation links nutrient sensing to downstream stress resistance. Our results reveal a novel regulatory connection between nutrient-sensitive glycosylation and NRF2 signaling, and provide a blueprint for future approaches to discover functionally important O-GlcNAcylation events on other KLHL family proteins in various experimental and disease contexts.
2017-06-26 | GSE81740 | GEO
Project description:The objectives of this study are to understand the regulatory roles of MAZ in biological processes using the NGS-deriveed ChIP-seq, DNA-MEDIP-seq and RNA-seq data in HAP1 control cells and MAZ knockout cells. Our comparative analysis of these data generated from the HAP1 control and MAZ KO cells shows that MAZ is required for recruiting STAT1 to its target sites by reshaping epigenetic landscape in the human genome, thereby mediating antiviral response cells. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for STAT1 and H3K4me3, H3K27Ac in HAP1 cells.
2024-03-25 | GSE215081 | GEO
Project description:We report that cellular O-GlcNAcylation levels decline along the course of megakaryocyte (MK) differentiation from human-derived hematopoietic stem and progenitor cells (HSPCs) and that inhibition of O-GlcNAc transferase (OGT), of which catalyzes O-GlcNAcylation, prolongedly decreases O-GlcNAcylation and induces megakaryopoiesis and thrombopoiesis. To gain the better insight into the potential mechanisms underlying platelet regulation by O-GlcNAcylation ,we compared the genome-wide transcription profiles of megakaryblastic MEG-01 cells with decreased O-GlcNAcylation (OGTi) and its control counterpart using RNA sequencing. Gene ontology and enrichment analysis of differentially expressed genes suggest that platelet formation might be regulated through the perturbation in cell adhesion molecules, i.e. integrin-a4 and b7, downstream of O-GlcNAc/c-Myc axis.
2020-08-06 | GSE150880 | GEO