Histone deacetylase inhibitor trichostatin A enhances myogenesis by coordinating muscle regulatory factors and myogenic repressors.
Histone deacetylase inhibitors (HDACIs) are known to promote skeletal muscle formation. However, their mechanisms that include effects on the expression of major muscle components such as the dystrophin-associated proteins complex (DAPC) or myogenic regulatory factors (MRFs) remain unknown. In this study, we investigated the effects of HDACIs on skeletal muscle formation using the C2C12 cell culture system. C2C12 myoblasts were exposed to trichostatin A (TSA), one of the most potent HDACIs, and differentiation was subsequently induced. We found that TSA enhances the expression of myosin heavy chain without affecting DAPC expression. In addition, TSA increases the expression of the early MRFs, Myf5 and MEF2, whereas it suppresses the expression of the late MRF, myogenin. Interestingly, TSA also enhances the expression of Id1, Id2, and Id3 (Ids). Ids are myogenic repressors that inhibit myogenic differentiation. These findings suggest that TSA promotes gene expression in proliferation and suppresses it in the differentiation stage of muscle formation. Taken together, our data demonstrate that TSA enhances myogenesis by coordinating the expression of MRFs and myogenic repressors.
Department of Neurology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Hiroki
H
Hagiwara
Fumiaki
F
Saito
Toshihiro
T
Masaki
Miki
M
Ikeda
Ayami
A
Nakamura-Ohkuma
Teruo
T
Shimizu
Kiichiro
K
Matsumura
D000818:Animals; D002460:Cell Line; D049028:Dystrophin-Associated Protein Complex / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000187:drug effects* / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism
D049028:Dystrophin-Associated Protein Complex; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; C067679:Idb3 protein, mouse; C012589:trichostatin A; D018995:Myosin Heavy Chains