Identification of a gene network contributing to hypertrophy in callipyge skeletal muscle

Vuocolo, Tony; Byrne, Keren; White, Jason D.; McWilliam, Sean; Reverter, Antônio; Cockett, Noelle E.; Tellam, Ross L.

doi:10.1152/physiolgenomics.00121.2006

Cited by 69 publications

(117 citation statements)

References 75 publications

(122 reference statements)

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“…Quantitative Real-time PCR (qRT-PCR)-The qRT-PCR procedure has been previously described (48). Expression was normalized to the housekeeping gene, GAPDH, which remained constant throughout the experiment (49).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-26a Targets the Histone Methyltransferase Enhancer of Zeste homolog 2 during Myogenesis

Wong

Tellam

2008

Journal of Biological Chemistry

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292

235

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MicroRNA (miRNA) are important regulators of many biological processes, but the targets for most miRNA are still poorly defined. In this study, we profiled the expression of miRNA during myogenesis, from proliferating myoblasts through to terminally differentiated myotubes. Microarray results identified six significantly differentially expressed miRNA that were more than 2-fold different in myotubes. From this list, miRNA-26a (miR-26a), an up-regulated miRNA, was further examined. Overexpression of miR-26a in murine myogenic C2C12 cells induced creatine kinase activity, an enzyme that markedly increases during myogenesis. Further, myoD and myogenin mRNA expression levels were also up-regulated. These results suggest that increased expression of miR-26a promotes myogenesis. Through a bioinformatics approach, we identified the histone methyltransferase, Enhancer of Zeste homolog 2 (Ezh2), as a potential target of miR-26a. Overexpression of miR-26a suppressed the activity of a luciferase reporter construct fused with the 3-untranslated region of Ezh2. In addition, miR-26a overexpression decreased Ezh2 mRNA expression. These results reveal a model of regulation during myogenesis whereby the up-regulation of miR-26a acts to post-transcriptionally repress Ezh2, a known suppressor of skeletal muscle cell differentiation.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-26a Targets the Histone Methyltransferase Enhancer of Zeste homolog 2 during Myogenesis

Wong

Tellam

2008

Journal of Biological Chemistry

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292

235

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“…This hypertrophy occurs primarily in the muscles of the pelvic limbs and loin and some muscles in the shoulder, which are enriched with a high proportion of type IIB fast-twitch glycolytic fibers (4). Although the molecular regulation of these hypertrophic processes is yet to be determined, Delta-like 1 homolog (DLK1) is found to be the causative protein (5)(6)(7)(8)(9)(10). The unique mode of inheritance of the CLPG phenotype has attracted a great deal of attention within the scientific community.…”

mentioning

confidence: 99%

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Gao

Chen

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Inheritance of the callipyge phenotype in sheep is an example of polar overdominance inheritance, an unusual mode of inheritance. To investigate the underlying molecular mechanism, we profiled the expression of the genes located in the Delta-like 1 homolog (Dlk1)-type III iodothyronine deiodinase (Dio3) imprinting region in mice. We found that the transcripts of the microRNA (miR) 379/miR-544 cluster were highly expressed in neonatal muscle and paralleled the expression of the Dlk1. We then determined the in vivo role of the miR-379/miR-544 cluster by establishing a mouse line in which the cluster was ablated. The maternal heterozygotes of young mutant mice displayed a hypertrophic tibialis anterior muscle, extensor digitorum longus muscle, gastrocnemius muscle, and gluteus maximus muscle and elevated expression of the DLK1 protein. Reduced expression of DLK1 was mediated by miR-329, a member of this cluster. Our results suggest that maternal expression of the imprinted miR-379/miR-544 cluster regulates paternal expression of the Dlk1 gene in mice. We therefore propose a miR-based molecular working model for polar overdominance inheritance. muscle hypertrophy | callipyge | DLK1 | miR-379/miR-544 cluster T he callipyge (CLPG) phenotype can be characterized by an increase in muscle mass due to muscular hypertrophy and a unique non-Mendelian mode of inheritance (1-3). CLPG individuals are born with normal muscle histology and develop muscle hypertrophy at ∼1 mo of age. This hypertrophy occurs primarily in the muscles of the pelvic limbs and loin and some muscles in the shoulder, which are enriched with a high proportion of type IIB fast-twitch glycolytic fibers (4). Although the molecular regulation of these hypertrophic processes is yet to be determined, Delta-like 1 homolog (DLK1) is found to be the causative protein (5-10). The unique mode of inheritance of the CLPG phenotype has attracted a great deal of attention within the scientific community. The CLPG offspring inherit the phenotype only when the mutated allele comes from the father and the wild-type allele from the mother (CLPG PAT /+ MAT ). CLPG PAT /CLPG MAT offspring exhibit a wild-type phenotype, despite carrying a CLPG mutation on the paternal chromosome. This unusual mode of inheritance led to the development of the genetic concept of polar overdominance (2, 11).The CLPG mutation has been mapped to the Dlk1-Dio3 imprinted domain, which spans ∼1 Mb and harbors at least three protein-encoding genes, including Dlk1, Peg11/Rtl1, and Dio3, and multiple noncoding RNA genes, including Gtl2, anti-Peg11/anti-Rtl1, Meg8, Mirg, C/D small nucleolar RNAs (snoRNAs), and microRNA clusters [the microRNA (miR) 379 and miR-127 clusters] (12-14). The coding genes are expressed paternally, whereas the noncoding genes are expressed maternally (15,16). Further analysis revealed a point mutation (A to G transition) within the intergenic region between the Dlk1 and Gtl2 genes of the imprinted Dlk1-Dio3 region (17, 18), which affects a muscle-specific, long-range cis-acting ...

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“…MyHC isoforms I, IIa and IIx have been detected at both the protein and mRNA levels in sheep skeletal muscle (Hemmings et al, 2009). MyHC IIb has been detected at the mRNA level in sheep muscle (Vuocolo et al, 2007), but it is not clear whether the protein is expressed. MyHC IIb mRNA but not the protein has been detected in certain human muscle fibers (Horton et al, 2001).…”

Section: Muscle Fiber Composition In Porcine Soleus and Edl Musclesmentioning

confidence: 99%

Correlation of forkhead box transcription factor O1 and myosin heavy chain isoforms in porcine skeletal muscle

et al. 2014

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ABSTRACT. We examined the expression of myosin heavy chain (MyHC) isoforms and forkhead box transcription factor O1 (FoxO1) in porcine soleus and extensor digitorum longus (EDL) muscles to clarify the correlation of FoxO1 and the relative abundance of transcripts of MyHC isoforms. Soleus muscle was found to be redder than EDL muscles in pigs, and immunohistochemical fast MyHC staining showed more oxidative type I fibers compared to EDL. qRT-PCR quantification of MyHC isoforms I, IIa, IIx, and IIb showed that expression of MyHC I and MyHC IIa mRNAs was much higher, whereas expression of MyHC IIx and MyHC IIb mRNAs was much lower in porcine soleus muscle compared to EDL muscle. Expression of FoxO1 mRNA and p-FoxO1 protein was significantly more abundant in porcine soleus muscle compared to EDL muscle. The expression of phosphorylated FoxO1 (p-FoxO1) was positively correlated with the expression of MyHC I (R = 0.9747, P < 0.01) and negatively correlated with the expression of MyHC IIx (R = -0.9963, P < 0.01) and MyHC IIb (R = -0.9834, P < 0.01). Taken together, these results suggested that FoxO1 may play a pivotal role in the determination of muscle fiber type.

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Identification of a gene network contributing to hypertrophy in callipyge skeletal muscle

Cited by 69 publications

References 75 publications

MicroRNA-26a Targets the Histone Methyltransferase Enhancer of Zeste homolog 2 during Myogenesis

MicroRNA-26a Targets the Histone Methyltransferase Enhancer of Zeste homolog 2 during Myogenesis

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Correlation of forkhead box transcription factor O1 and myosin heavy chain isoforms in porcine skeletal muscle

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