Requirement of decreased O-GlcNAc glycosylation of Mef2D for its recruitment to the myogenin promoter

Ogawa, Masamichi; Sakakibara, Yohei; Kamemura, Kazuo

doi:10.1016/j.bbrc.2013.03.033

Cited by 23 publications

(18 citation statements)

References 21 publications

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“…However, many independent studies have recently focused on the numerous roles of glycoconjugates during myogenesis [102]. The results of these studies have indicated that the expression of MyoG is partly regulated by the reduced glycosylation-dependent recruitment of Mef2D to MyoG promoter, suggesting negative regulatory mechanisms of skeletal muscle development by O-GlcNAc glycosylation [103].…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Differentially Expressed in Myogenin Knock-Down Bovine Muscle Satellite Cells during Differentiation through RNA Sequencing Analysis

et al. 2014

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BackgroundThe expression of myogenic regulatory factors (MRFs) consisting of MyoD, Myf5, myogenin (MyoG) and MRF4 characterizes various phases of skeletal muscle development including myoblast proliferation, cell-cycle exit, cell fusion and the maturation of myotubes to form myofibers. Although it is well known that the function of MyoG cannot be compensated for other MRFs, the molecular mechanism by which MyoG controls muscle cell differentiation is still unclear. Therefore, in this study, RNA-Seq technology was applied to profile changes in gene expression in response to MyoG knock-down (MyoGkd) in primary bovine muscle satellite cells (MSCs).ResultsAbout 61–64% of the reads of over 42 million total reads were mapped to more than 13,000 genes in the reference bovine genome. RNA-Seq analysis identified 8,469 unique genes that were differentially expressed in MyoGkd. Among these genes, 230 were up-regulated and 224 were down-regulated by at least four-fold. DAVID Functional Annotation Cluster (FAC) and pathway analysis of all up- and down-regulated genes identified overrepresentation for cell cycle and division, DNA replication, mitosis, organelle lumen, nucleoplasm and cytosol, phosphate metabolic process, phosphoprotein phosphatase activity, cytoskeleton and cell morphogenesis, signifying the functional implication of these processes and pathways during skeletal muscle development. The RNA-Seq data was validated by real time RT-PCR analysis for eight out of ten genes as well as five marker genes investigated.ConclusionsThis study is the first RNA-Seq based gene expression analysis of MyoGkd undertaken in primary bovine MSCs. Computational analysis of the differentially expressed genes has identified the significance of genes such as SAP30-like (SAP30L), Protein lyl-1 (LYL1), various matrix metalloproteinases, and several glycogenes in myogenesis. The results of the present study widen our knowledge of the molecular basis of skeletal muscle development and reveal the vital regulatory role of MyoG in retaining muscle cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Identification of Genes Differentially Expressed in Myogenin Knock-Down Bovine Muscle Satellite Cells during Differentiation through RNA Sequencing Analysis

et al. 2014

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“…As skeletal muscle is the major organ in exercise and glucose metabolism, skeletal muscle function, such as skeletal muscle contraction [14], myogenin protein content and myogenesis [15], has been suggested to be associated with O-GlcNAc signalling. Furthermore, higher levels of O-GlcNAcylation are associated with protein degradation and muscle atrophy [16].…”

Section: Introductionmentioning

confidence: 99%

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

et al. 2016

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Aims/hypothesis O-GlcNAcylation is implicated in modulating mitochondrial function, which is closely involved in regulating muscle metabolism. The presence of O-GlcNAcase (OGA), the enzyme involved in the removal of O-GlcNAc, in mitochondria was recently confirmed in rats. In the present study, we investigated the regulation of myogenesis and muscle insulin sensitivity to OGA in mice, with a focus on mitochondria. Methods C57BL/6J mice fed a high-fat diet for 4 months were used to observe mitochondrial density, activity and O-GlcNAcylation in muscle. Small interfering RNA and overexpression vectors were used to modulate protein content in vitro. Results High-fat feeding decreased the OGA level and largely increased mitochondrial O-GlcNAcylation in mouse skeletal muscle that was accompanied by decreased levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), decreased mitochondrial density and disrupted mitochondrial complex activities. Knockdown of OGA in C2C12 myoblasts promoted PGC-1α degradation, resulting in the suppression of mitochondrial biogenesis and myogenesis, whereas neither knockdown of O-GlcNAc transferase nor overexpression of OGA had significant effects on myogenesis. Mitochondrial dysfunction as evidenced by decreased ATP content and increased reactive oxygen species production, and increased lipid and protein oxidation was observed in both myoblasts and myotubes after OGA knockdown. Meanwhile, elevated O-GlcNAcylation through either OGA knockdown or treatment with the OGA inhibitor PUGNAc and the O-GlcNAc transferase substrate D-GlcNAc suppressed myotube insulin signalling transduction and glucose uptake. OGA overexpression had no significant effect on insulin sensitivity but sufficiently improved the insulin resistance induced by D-GlcNAc treatment. Conclusions/interpretation These data suggest that OGA can modulate mitochondrial density via PGC-1α and mitochondrial function via protein O-GlcNAcylation. In this manner, OGA appears to play a key role in myogenesis and the development of muscle insulin resistance.

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“…Contrary to its positive effect on gene transcription, O-GlcNAc has also recently been shown to negatively regulate the terminal differentiation of skeletal muscle through glycosylation of Mef2D, a transcriptional activator of myogenin [33]. Furthermore, we recently reported that increased O-GlcNAc levels are associated with a blunting of the cardiac hypertrophic responses [8].…”

Section: Ogt and Epigenetics/transcriptionmentioning

confidence: 99%

The Role of O-GlcNAc Transferase in Regulating the Gene Transcription of Developing and Failing Hearts

Medford

Marsh

2014

Future Cardiol.

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Heart failure treatment currently centers on symptom management, primarily through reductions in systemic blood pressure and fluid retention. The O-linked attachment of β-N-acetylglucosamine to cardiac proteins is increased in cardiovascular disease and heart failure, and O-GlcNAc transferase (OGT) is the enzyme that catalyzes this addition. Deletion of OGT is embryonically lethal, and cardiomyocyte-specific OGT knockdown causes the exacerbation of heart failure. Stem cell therapy is currently a major focus of heart failure research, and it was recently discovered that OGT is intricately involved with stem cell differentiation. This article focuses on the relationship of OGT with epigenetics and pluripotency, and integrates OGT with several emerging areas of heart failure research, including calcium signaling.

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Requirement of decreased O-GlcNAc glycosylation of Mef2D for its recruitment to the myogenin promoter

Cited by 23 publications

References 21 publications

Identification of Genes Differentially Expressed in Myogenin Knock-Down Bovine Muscle Satellite Cells during Differentiation through RNA Sequencing Analysis

Identification of Genes Differentially Expressed in Myogenin Knock-Down Bovine Muscle Satellite Cells during Differentiation through RNA Sequencing Analysis

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis

The Role of O-GlcNAc Transferase in Regulating the Gene Transcription of Developing and Failing Hearts

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