Small RNA-Mediated Epigenetic Myostatin Silencing

Myostatin (Mstn) is a secreted growth factor that negatively regulates muscle mass and is therefore a potential pharmacological target for the treatment of muscle wasting disorders such as Duchenne muscular dystrophy. Here we describe a novel Mstn blockade approach in which small interfering RNAs (s...

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Bibliographic Details
Main Authors: Thomas C Roberts (Author), Samir EL Andaloussi (Author), Kevin V Morris (Author), Graham McClorey (Author), Matthew JA Wood (Author)
Format: Book
Published: Elsevier, 2012-01-01T00:00:00Z.
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100 1 0 |a Thomas C Roberts  |e author 
700 1 0 |a Samir EL Andaloussi  |e author 
700 1 0 |a Kevin V Morris  |e author 
700 1 0 |a Graham McClorey  |e author 
700 1 0 |a Matthew JA Wood  |e author 
245 0 0 |a Small RNA-Mediated Epigenetic Myostatin Silencing 
260 |b Elsevier,   |c 2012-01-01T00:00:00Z. 
500 |a 2162-2531 
500 |a 10.1038/mtna.2012.15 
520 |a Myostatin (Mstn) is a secreted growth factor that negatively regulates muscle mass and is therefore a potential pharmacological target for the treatment of muscle wasting disorders such as Duchenne muscular dystrophy. Here we describe a novel Mstn blockade approach in which small interfering RNAs (siRNAs) complementary to a promoter-associated transcript induce transcriptional gene silencing (TGS) in two differentiated mouse muscle cell lines. Silencing is sensitive to treatment with the histone deacetylase inhibitor trichostatin A, and the silent state chromatin mark H3K9me2 is enriched at the Mstn promoter following siRNA transfection, suggesting epigenetic remodeling underlies the silencing effect. These observations suggest that long-term epigenetic silencing may be feasible for Mstn and that TGS is a promising novel therapeutic strategy for the treatment of muscle wasting disorders. 
546 |a EN 
690 |a epigenetic 
690 |a muscle degeneration 
690 |a myostatin 
690 |a siRNA 
690 |a transcriptional gene silencing 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Molecular Therapy: Nucleic Acids, Vol 1, Iss C (2012) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2162253116300804 
787 0 |n https://doaj.org/toc/2162-2531 
856 4 1 |u https://doaj.org/article/1a5b9914b7f84a9a95242b647a634a0c  |z Connect to this object online.