Histone deacetylase inhibitor trichostatin A enhances myogenesis by coordinating muscle regulatory factors and myogenic repressors |
| |
Authors: | Hagiwara Hiroki Saito Fumiaki Masaki Toshihiro Ikeda Miki Nakamura-Ohkuma Ayami Shimizu Teruo Matsumura Kiichiro |
| |
Institution: | aDepartment of Neurology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan;bDepartment of Medical Science, Teikyo University of Science, 2-2-1 Senjusakuragi, Adachi-ku, Tokyo 120-0045, Japan |
| |
Abstract: | 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. |
| |
Keywords: | Abbreviations: HDACIs histone deacetylase inhibitors TSA Trichostatin A MRFs myogenic regulatory factors DAPC dystrophin-associated proteins complex MHC myosin heavy chain |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|