Browse > Article
http://dx.doi.org/10.14348/molcells.2015.2278

HDAC4 Regulates Muscle Fiber Type-Specific Gene Expression Programs  

Cohen, Todd J. (Department of Pharmacology and Cancer Biology, Duke University)
Choi, Moon-Chang (Department of Pharmacology and Cancer Biology, Duke University)
Kapur, Meghan (Department of Pharmacology and Cancer Biology, Duke University)
Lira, Vitor A. (Department of Medicine, Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia)
Yan, Zhen (Department of Medicine, Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia)
Yao, Tso-Pang (Department of Pharmacology and Cancer Biology, Duke University)
Abstract
Fiber type-specific programs controlled by the transcription factor MEF2 dictate muscle functionality. Here, we show that HDAC4, a potent MEF2 inhibitor, is predominantly localized to the nuclei in fast/glycolytic fibers in contrast to the sarcoplasm in slow/oxidative fibers. The cytoplasmic localization is associated with HDAC4 hyper-phosphorylation in slow/oxidative-fibers. Genetic reprogramming of fast/glycolytic fibers to oxidative fibers by active CaMKII or calcineurin leads to increased HDAC4 phosphorylation, HDAC4 nuclear export, and an increase in markers associated with oxidative fibers. Indeed, HDAC4 represses the MEF2-dependent, PGC-$1{\alpha}$-mediated oxidative metabolic gene program. Thus differential phosphorylation and localization of HDAC4 contributes to establishing fiber type-specific transcriptional programs.
Keywords
fiber type; HDAC4; MEF2; PGC-$1{\alpha}$;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Wu, H., Kanatous, S.B., Thurmond, F.A., Gallardo, T., Isotani, E., Bassel-Duby, R., and Williams, R.S. (2002). Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296, 349-352.   DOI   ScienceOn
2 Wu, H., Naya, F.J., McKinsey, T.A., Mercer, B., Shelton, J.M., Chin, E.R., Simard, A.R., Michel, R.N., Bassel-Duby, R., Olson, E.N., et al. (2000). MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. EMBO J. 19, 1963-1973.   DOI   ScienceOn
3 Wu, H., Rothermel, B., Kanatous, S., Rosenberg, P., Naya, F.J., Shelton, J.M., Hutcheson, K.A., DiMaio, J.M., Olson, E.N., Bassel-Duby, R., et al. (2001). Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway. EMBO J.20, 6414-6423.   DOI   ScienceOn
4 Zhao, X., Ito, A., Kane, C.D., Liao, T.S., Bolger, T.A., Lemrow, S.M., Means, A.R., and Yao, T.P. (2001). The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking. J. Biol. Chem. 276, 35042-35048.   DOI   ScienceOn
5 Akimoto, T., Ribar, T.J., Williams, R.S., and Yan, Z. (2004a). Skeletal muscle adaptation in response to voluntary running in $Ca^{2+}$calmodulin-dependent protein kinase IV-deficient mice. Am. J. Physiol. Cell Physiol. 287, C1311-1319.   DOI   ScienceOn
6 Akimoto, T., Sorg, B.S., and Yan, Z. (2004b). Real-time imaging of peroxisome proliferator-activated receptor-gamma coactivator-1alpha promoter activity in skeletal muscles of living mice. Am. J. Physiol. Cell Physiol. 287, C790-796.   DOI   ScienceOn
7 Backs, J., Song, K., Bezprozvannaya, S., Chang, S., and Olson, E.N. (2006). CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J. Clin. Invest. 116, 1853-1864.   DOI   ScienceOn
8 Bassel-Duby, R., and Olson, E.N. (2006). Signaling pathways in skeletal muscle remodeling. Ann. Rev. Biochem. 75, 19-37.   DOI   ScienceOn
9 Black, B.L., and Olson, E.N. (1998). Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Annu. Rev. Cell Dev. Biol. 14, 167-196.   DOI   ScienceOn
10 Chin, E.R., Olson, E.N., Richardson, J.A., Yang, Q., Humphries, C., Shelton, J.M., Wu, H., Zhu, W., Bassel-Duby, R., and Williams, R.S. (1998). A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 12, 2499-2509.   DOI   ScienceOn
11 Choi, M.C., Cohen, T.J., Barrientos, T., Wang, B., Li, M., Simmons, B.J., Yang, J.S., Cox, G.A., Zhao, Y., and Yao, T.P. (2012). A direct HDAC4-MAP kinase crosstalk activates muscle atrophy program. Mol. Cell 47, 122-132.   DOI   ScienceOn
12 Fitzsimons, D.P., Diffee, G.M., Herrick, R.E., and Baldwin, K.M. (1990). Effects of endurance exercise on isomyosin patterns in fast- and slow-twitch skeletal muscles. J. Appl. Physiol. 68, 1950-1955.   DOI
13 Cohen, T.J., Waddell, D.S., Barrientos, T., Lu, Z., Feng, G., Cox, G.A., Bodine, S.C., and Yao, T.P. (2007). The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. J. Biol. Chem. 282, 33752-33759.   DOI   ScienceOn
14 Cohen, T.J., Barrientos, T., Hartman, Z.C., Garvey, S.M., Cox, G.A., and Yao, T.P. (2009). The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity. FASEB J. 23, 99-106.   DOI   ScienceOn
15 Czubryt, M.P., McAnally, J., Fishman, G.I., and Olson, E.N. (2003). Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha ). and mitochondrial function by MEF2 and HDAC5. Proc. Natl. Acad. Sci. USA 100, 1711-1716.   DOI   ScienceOn
16 Lin, J., Wu, H., Tarr, P.T., Zhang, C.Y., Wu, Z., Boss, O., Michael, L.F., Puigserver, P., Isotani, E., Olson, E.N., et al. (2002). Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418, 797-801.   DOI   ScienceOn
17 Liu, Y., Randall, W.R., and Schneider, M.F. (2005). Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle. J. Cell Biol. 168, 887-897.   DOI   ScienceOn
18 Marin, P., Andersson, B., Krotkiewski, M., and Bjorntorp, P. (1994). Muscle fiber composition and capillary density in women and men with NIDDM. Diabetes Care 17, 382-386.   DOI   ScienceOn
19 McKinsey, T.A., Zhang, C.L., and Olson, E.N. (2002). MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem. Sci. 27, 40-47.   DOI   ScienceOn
20 McKinsey, T.A., Zhang, C.L., Lu, J., and Olson, E.N. (2000). Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408, 106-111.   DOI   ScienceOn
21 Minetti, G.C., Colussi, C., Adami, R., Serra, C., Mozzetta, C., Parente, V., Fortuni, S., Straino, S., Sampaolesi, M., Di Padova, M., et al. (2006). Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat. Med. 12, 1147-1150.   DOI   ScienceOn
22 Naya, F.J., Mercer, B., Shelton, J., Richardson, J.A., Williams, R.S., and Olson, E.N. (2000). Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. J. Biol. Chem. 275, 4545-4548.   DOI   ScienceOn
23 Nyholm, B., Qu, Z., Kaal, A., Pedersen, S.B., Gravholt, C.H., Andersen, J.L., Saltin, B., and Schmitz, O. (1997). Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM. Diabetes 46, 1822-1828.   DOI
24 Pette, D. (2002). The adaptive potential of skeletal muscle fibers. Can. J. Appl. Physiol. 27, 423-448.   DOI   ScienceOn
25 Potthoff, M.J., Arnold, M.A., McAnally, J., Richardson, J.A., Bassel-Duby, R., and Olson, E.N. (2007a). Regulation of skeletal muscle sarcomere integrity and postnatal muscle function by Mef2c. Mol. Cell. Biol. 27, 8143-8151.   DOI   ScienceOn
26 Schrauwen, P., and Hesselink, M.K. (2004). Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 53, 1412-1417.   DOI   ScienceOn
27 Potthoff, M.J., Wu, H., Arnold, M.A., Shelton, J.M., Backs, J., McAnally, J., Richardson, J.A., Bassel-Duby, R., and Olson, E.N. (2007b). Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J. Clin. Invest. 117, 2459-2467.   DOI
28 Russell, A.P., Feilchenfeldt, J., Schreiber, S., Praz, M., Crettenand, A., Gobelet, C., Meier, C.A., Bell, D.R., Kralli, A., Giacobino, J.P., et al. (2003). Endurance training in humans leads to fiber typespecific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferatoractivated receptor-alpha in skeletal muscle. Diabetes 52, 2874-2881.   DOI   ScienceOn
29 Sandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z.P., Lecker, S.H., Goldberg, A.L., and Spiegelman, B.M. (2006). PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc. Natl. Acad. Sci. USA 103, 16260-16265.   DOI   ScienceOn
30 Spangenburg, E.E., and Booth, F.W. (2003). Molecular regulation of individual skeletal muscle fibre types. Acta Physiol. Scand 178, 413-424.   DOI   ScienceOn
31 Terada, S., Goto, M., Kato, M., Kawanaka, K., Shimokawa, T., and Tabata, I. (2002). Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem. Biophys. Res. Commun. 296, 350-354.   DOI   ScienceOn
32 Vega, R.B., Harrison, B.C., Meadows, E., Roberts, C.R., Papst, P.J., Olson, E.N., and McKinsey, T.A. (2004). Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5. Mol. Cell. Biol. 24, 8374-8385.   DOI   ScienceOn