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Exercise increases the binding of MEF 2A to the Cpt1b promoter in mouse skeletal muscle
Author(s) -
Yuan H.,
Niu Y.,
Liu X.,
Fu L.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12395
Subject(s) - histone deacetylase 5 , endocrinology , medicine , skeletal muscle , mef2 , biology , chromatin immunoprecipitation , microbiology and biotechnology , histone , histone deacetylase , gene expression , promoter , biochemistry , gene , enhancer
Aim Muscle‐type carnitine palmitoyltransferase 1 ( CPT 1b) plays an important role in skeletal muscle mitochondrial fatty acid β ‐oxidation. A myocyte‐specific enhancer factor ( MEF 2) site that binds MEF 2A in the promoter of Cpt1b has been identified. The aim of this study is to determine whether Cpt1b expression is regulated by MEF 2 in response to exercise training. Methods Twelve male, 14‐week‐old C57 BL /6 mice underwent 6 weeks of treadmill exercise at 12 m min −1 , for 60 min day −1 , 5 days week −1 . Quadriceps muscles were analysed by real‐time PCR , Western blot, chromatin immunoprecipitation. Results The binding of MEF2A to the Cpt1b promoter was elevated in the quadriceps muscle of mice after 6‐week aerobic exercise intervention. The repressor partner of MEF2, histone deacetylase 5 (HDAC5), binding to the Cpt1b promoter was decreased by exercise training. In C2C12 myoblast, MEF2A overexpression increased the Cpt1b mRNA expression and the Cpt1b promoter transcriptional activity, which were suppressed by HDAC5. Moreover, exercise training induced MEF2A hyperacetylation, which is strongly associated with its enhanced DNA‐binding ability. The binding of both HDAC5 and histone deacetylase 3 (HDAC3) to MEF2A was decreased by exercise training. Overexpression of HDAC5 decreased exogenous MEF2A acetylation level with an increased binding of endogenous HDAC3 to MEF2A. Finally, the phosphorylation levels of HDAC5 Ser259 and Ser498 were increased by exercise training. Exercise training decreased the abundance of HDAC5 in the nucleus while increasing its abundance in the cytoplasm. Conclusion Our results indicated that exercise‐induced CPT 1b expression was at least in part mediated by HDAC 5/ MEF 2A interaction.