Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174100 | ENA |
REPOSITORIES: ENA
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Project description:In the present study we have studied the mechanistic and functional aspects of NCoR1 function in mouse skeletal muscle. NCoR1 muscle-specific knockout mice exhibited an increased oxidative metabolism. Global gene expression analysis revealed a high overlap between the effects of NCoR1 deletion and peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) overexpression on oxidative metabolism in skeletal muscle. The repressive effect of NCoR1 on oxidative phosphorylation gene expression specifically antagonizes PGC-1alpha-mediated coactivation of ERRalpha. We therefore delineated the molecular mechanism by which a transcriptional network controlled by corepressor and coactivator proteins determines the metabolic properties of skeletal muscle, thus representing a potential therapeutic target for metabolic diseases. Gene expression of a total of 20 gastrocnemius samples from control (CON, n = 5), NCoR1 muscle-specific knockout (NCoR1 MKO, n = 5), wild type (WT, n = 5) and PGC-1alpha muscle-specific transgenic (PGC-1alpha mTg, n = 5) adult male mice was analyzed using GeneChip® Gene 1.0 ST Array System (Affymetrix). NCoR1 MKO and PGC-1alpha mTg samples were compared to CON and WT samples, respectively.
2013-01-08 | E-GEOD-40439 | biostudies-arrayexpress
Project description:In the present study we have studied the mechanistic and functional aspects of NCoR1 function in mouse skeletal muscle. NCoR1 muscle-specific knockout mice exhibited an increased oxidative metabolism. Global gene expression analysis revealed a high overlap between the effects of NCoR1 deletion and peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) overexpression on oxidative metabolism in skeletal muscle. The repressive effect of NCoR1 on oxidative phosphorylation gene expression specifically antagonizes PGC-1alpha-mediated coactivation of ERRalpha. We therefore delineated the molecular mechanism by which a transcriptional network controlled by corepressor and coactivator proteins determines the metabolic properties of skeletal muscle, thus representing a potential therapeutic target for metabolic diseases.
2013-01-08 | GSE40439 | GEO
Project description:Title: Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin Sensitivity Abstract: Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1α-/- βf/f/MLC-Cre mice) were generated and characterized. PGC-1α-/-βf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1α- or PGC-1β-deficient mice and wild-type controls. The exercise phenotype of the PGC-1α-/-βf/f/MLC-Cre mice was associated with a marked diminution in muscle oxidative capacity and mitochondrial structural derangements consistent with fusion/fission and biogenic defects together with rapid depletion of muscle glycogen stores during exercise. Surprisingly, the skeletal muscle fiber type profile of the PGC-1α-/-βf/f/MLCCre mice was not significantly different than the wild-type mice. Moreover, insulin sensitivity and glucose tolerance were also not altered in the PGC-1α-/-βf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity. RNA from PGC-1alpha-/- beta f/f/Mlc1fcre was obtained and gene expression pattern compared with PGC-1alpha -/-, PGC-1beta f/f, and PGC-1beta f/f/Mlc1fCre controls. Results file descriptions: 1. GSE23365_skfloxAKO_PPexcl_genesup_GEO-8-16-2010: This table contains genes that were upregulated ≥2.0 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names. 2. GSE23365_skfloxAKO_PPexcl_genesdown_GEO-8-16-2010 This table contains genes that were downregulated ≤0.7 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column “description’ contains the gene name, and the column “ID” contains Agilent probe names.
2010-12-01 | E-GEOD-23365 | biostudies-arrayexpress
Project description:Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling. Gastrocnemius muscle mRNA from young (10 week old) and old (24 month old) wild-type and knock-out (muscle-specific PGC-1alpha, myogenin-cre) C57Bl/6N/6J/129 mice
2013-12-05 | E-GEOD-52550 | biostudies-arrayexpress
Project description:Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling.
2013-12-05 | GSE52550 | GEO
Project description:PGC-1alpha has been proposed to couple gene transcription and RNA processing via SR-rich domains and an RNA recognition motif located at the C-terminal domain (CTD). However, the full extent by which the CTD of PGC-1alpha regulates its function in gene expression and RNA processing remains largely unknown. Here, we used RNA-seq to evaluate the effects of CTD deletion (dCTD) on PGC-1alpha function. We found that deletion of the CTD of PGC-1alpha virtually abolished its effects on transcriptome remodeling and the resulting increase in oxidative capacity in skeletal muscle cells. Moreover, we implemented in vitro affinity purification followed by sequencing (in vitro AP-seq), which revealed more than 700 RNAs bound to the CTD of PGC-1alpha. The majority of these RNAs were transcribed at DNA regulatory elements such as promoters and distal intergenic regions. These results demonstrate that PGC-1alpha function is highly modulated at the CTD via multivalent protein-RNA interactions.
2021-09-04 | GSE156593 | GEO
Project description:PGC-1alpha has been proposed to couple gene transcription and RNA processing via SR-rich domains and an RNA recognition motif located at the C-terminal domain (CTD). However, the full extent by which the CTD of PGC-1alpha regulates its function in gene expression and RNA processing remains largely unknown. Here, we used RNA-seq to evaluate the effects of CTD deletion (dCTD) on PGC-1alpha function. We found that deletion of the CTD of PGC-1alpha virtually abolished its effects on transcriptome remodeling and the resulting increase in oxidative capacity in skeletal muscle cells. Moreover, we implemented in vitro affinity purification followed by sequencing (in vitro AP-seq), which revealed more than 700 RNAs bound to the CTD of PGC-1alpha. The majority of these RNAs were transcribed at DNA regulatory elements such as promoters and distal intergenic regions. These results demonstrate that PGC-1alpha function is highly modulated at the CTD via multivalent protein-RNA interactions.
2021-09-04 | GSE156592 | GEO
Project description:Microarray skeletal muscle PGC-1alpha-/- - beta f/f/Mlc1fCre mice
| PRJNA131245 | ENA
Project description:We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle. As our study revealed regulation of HSF1 by PGC-1alpha, in some experiments we knocked-down HSF1 using siRNAs in addition to inducing PGC-1alpha expression. Cells were grown in 24-well plates and adenoviruses encoding either GFP ("Ad-GFP"), PGC-1alpha ("Ad-PGC-1alpha") or PGC-1beta ("Ad-PGC-1beta") were directly added to the culture medium. For experiments involving siRNA transfections, cells were transfected with the indicated siRNAs 48hr prior to infection with adenoviruses encoding either GFP ("Ad-GFP") or PGC-1alpha ("Ad-PGC-1alpha").
2015-09-19 | E-GEOD-51498 | biostudies-arrayexpress
Project description:We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle. As our study revealed regulation of HSF1 by PGC-1alpha, in some experiments we knocked-down HSF1 using siRNAs in addition to inducing PGC-1alpha expression.
2015-09-19 | GSE51498 | GEO