Genome-wide map of histone H3 lysine 36 tri-methylation in wild type mouse myocytes and myocytes bearing a muscle-specific H19/Igf2 enhancer deletion
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71227 | GEO | 2018/07/20
REPOSITORIES: GEO
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Project description:Functional data indicate that specific histone modification enzymes can be key to longevity in Caenorhabditis elegans, but epigenetic mechanisms of lifespan regulation are not well understood. In this study, we profiled the genome-wide pattern of tri-methylation of lysine 36 on histone 3 (H3K36me3) in the somatic cells of young and old C. elegans. We revealed a new role of H3K36me3 in maintaining gene expression stability through aging with important consequence on longevity. We found that genes with dramatic expression change during aging are marked with low or even undetectable levels of H3K36me3 in their gene-bodies, irrespective of their corresponding mRNA abundance. Importantly, inactivation of the methyltransferase met-1 resulted in a decrease in global H3K36me3 marks, an increase in mRNA expression change with age, and a shortened lifespan, suggesting a causative role of the H3K36me3 marking in modulating age-dependent gene expression stability and longevity.
2015-04-01 | GSE62720 | GEO
Project description:Functional data indicate that specific histone modification enzymes can be key to longevity in Caenorhabditis elegans, but epigenetic mechanisms of lifespan regulation are not well understood. In this study, we profiled the genome-wide pattern of tri-methylation of lysine 36 on histone 3 (H3K36me3) in the somatic cells of young and old C. elegans. We revealed a new role of H3K36me3 in maintaining gene expression stability through aging with important consequence on longevity. We found that genes with dramatic expression change during aging are marked with low or even undetectable levels of H3K36me3 in their gene-bodies, irrespective of their corresponding mRNA abundance. Importantly, inactivation of the methyltransferase met-1 resulted in a decrease in global H3K36me3 marks, an increase in mRNA expression change with age, and a shortened lifespan, suggesting a causative role of the H3K36me3 marking in modulating age-dependent gene expression stability and longevity. We performed genome-wide mapping of histone H3 and H3K36me3 in young (D2A) and old (D12A) C.elegans somatic cells by ChIP-seq in glp-1(e2141). mRNA-seq was performed in young (D2A) and old (D12A) glp-1(e2141) somatic cells to identify mRNA expression change during aging from D2A to D12A.
2015-04-01 | E-GEOD-62720 | biostudies-arrayexpress
Project description:Background: Skeletal muscle myocytes have evolved into slow and fast-twitch types. These types are functionally distinct as a result of differential gene and protein expression. However, an understanding of the complexity of gene and protein variation between myofibers is unknown. Methods: We performed deep, whole cell, single cell RNA-seq on intact and fragments of skeletal myocytes from the mouse flexor digitorum brevis muscle. We compared the genomic expression data of 171 of these cells with two human proteomic datasets. The first was a spatial proteomics survey of mosaic patterns of protein expression utilizing the Human Protein Atlas (HPA) and the HPASubC tool. The second was a mass-spectrometry (MS) derived proteomic dataset of single human muscle fibers. Immunohistochemistry and RNA-ISH were used to understand variable expression. Results: scRNA-seq identified three distinct clusters of myocytes (a slow/fast 2A cluster and two fast 2X clusters). Utilizing 1,605 mosaic patterned proteins from visual proteomics, and 596 differentially expressed proteins by MS methods, we explore this fast 2X division. Only 36 genes/proteins were mosaic across all three studies, of which nine are newly described as variable between fast/slow twitch myofibers. An additional 414 genes/proteins were identified by two methods. Immunohistochemistry and RNA-ISH generally validated variable expression across methods presumably due to species-related differences. Conclusions: In this first integrated proteogenomic analysis of mature skeletal muscle myocytes we validate the main fiber types and greatly expand the known repertoire of twitch-type specific genes/proteins. We also demonstrate the importance of integrating genomic and proteomic datasets.
2020-01-15 | GSE143636 | GEO
Project description:Skeletal muscle is a major site of postprandial glucose disposal. Inadequate insulin action in this tissue contributes to hyperglycemia in type 1 and type 2 diabetes. While glucose is known to stimulate insulin secretion by pancreatic b cells, whether it directly engages nutrient-sensing pathways in skeletal muscle to regulate glucose metabolism remains largely unexplored. Here we identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improves postprandial glucose disposal in mice, whereas the muscle-specific ablation impaired insulin action and led to glucose intolerance. Mechanistically, glucose triggers a rapid calcium response in myocytes that acts on the class IIa histone deacetylase HDAC5, leading to Baf60c induction and insulin-independent AKT activation. The pathway is engaged by the anti-diabetic drugs sulfonylureas, suggesting that its therapeutic activation may have beneficial effects on glycemic control in diabetes. We used microarrays to elucidate the role of of Baf60c in transcriptional regulation by glucose in skeletal myocytes.
2017-04-20 | GSE79925 | GEO
Project description:Proteogenomic single cell analysis of skeletal muscle myocytes
| PRJNA601156 | ENA
Project description:Skeletal myocytes are metabolically active and susceptible to insulin resistance, thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network-context to integrate high-throughput data. We generated myocyte-specific RNA-seq data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the down-regulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D. Isolated skeletal muscle precursor cells from six normal glucose tolerant and non-obese males and females were differentiated in vitro. RNA from fully differentiated myotubes was sequenced using RNA-seq.
2015-04-07 | E-GEOD-63887 | biostudies-arrayexpress
Project description:Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). Obesity is tightly associated with T2D, making it challenging to isolate specific effects attributed to the disease alone. By using an in vitro myocyte model system we were able to isolate the inherent properties retained in myocytes originating from donor muscle precursor cells, without being confounded by varying extracellular factors present in the in vivo environment of the donor. We generated and characterized transcriptional profiles of myocytes from 24 human subjects, using a factorial design with two levels each of the factors T2D (healthy or diseased) and obesity (non-obese or obese), and determined the influence of each specific factor on genome-wide transcription. We identified a striking similarity of the transcriptional profiles associated independently with T2D or obesity. Obesity thus presents an inherent phenotype in skeletal myocytes, similar to that induced by T2D. Through bioinformatics analysis we found a candidate epigenetic mechanism, H3K27me3 histone methylation, mediating the observed transcriptional signatures. Functional characterization of the expression profiles revealed dysregulated myogenesis and down-regulated muscle function in connection with T2D and obesity, as well as up-regulation of genes involved in inflammation and the extracellular matrix. Further on, we identified a metabolite subnetwork involved in sphingolipid metabolism and affected by transcriptional up-regulation in T2D. Collectively, these findings pinpoint transcriptional changes that are hard-wired in skeletal myocytes in connection with both obesity and T2D.
2017-04-22 | GSE81965 | GEO
Project description:Investigate the transcriptional landscape changes promoted by Nr2f6 knockdown in C2C12 myocytes. We performed RNA-seq analysis in control non-target (siScr) and siNr2f6 transfected myocytes.
2024-04-05 | GSE229102 | GEO
Project description:Skeletal myocytes are metabolically active and susceptible to insulin resistance, thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network-context to integrate high-throughput data. We generated myocyte-specific RNA-seq data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the down-regulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D.
2015-04-07 | GSE63887 | GEO
Project description:Title: Changes in gene expression affected by H2O2 in cardiac myocytes.<br/> Description: We aim to identify the changes in gene expression in response to <br/> oxidative stress in rat neonatal ventricular myocytes.<br/> Oxidative stress will be induced by dosing neonatal ventricular myocyte<br/> cultures with 0.2, 0.1 and 0.04mM hydrogen peroxide at 2, 4 and 8 hr time<br/> points using unstimulated myocytes as control.
2011-11-08 | E-MIMR-12 | biostudies-arrayexpress