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Gene Review

MEF2A  -  myocyte enhancer factor 2A

Homo sapiens

Synonyms: ADCAD1, MEF2, Myocyte-specific enhancer factor 2A, RSRFC4, RSRFC9, ...
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Disease relevance of MEF2A

  • In addition, it is speculated that p300 might modulate the activity of the TR-RxR-MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A [1].
  • RECENT FINDINGS: Positional cloning based on genome-wide linkage analysis with large families identified the first non - lipid-related disease-causing gene, MEF2A (encoding a transcriptional factor), for coronary artery disease and myocardiaI infarction [2].
  • These results identify a pathogenic gene for a familial vascular disease with features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of CAD/MI [3].
  • The myocyte enhancer factor 2 (MEF2) family of transcription factors is not only important for controlling gene expression in normal cellular programs, like muscle differentiation, T-cell apoptosis, neuronal survival, and synaptic differentiation, but has also been linked to cardiac hypertrophy and other pathological conditions [4].
  • We examined the expression of the MEF2 genes in mouse embryonal carcinoma P19 cells before and after in vitro muscle differentiation induced by dimethyl sulfoxide (DMSO) [5].

High impact information on MEF2A

  • Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins [6].
  • This cooperativity required direct interactions between the DNA-binding domains of MEF2 and the myogenic bHLH factors, but only one of the factors needed a transactivation domain, and only one of the factors needed to be bound to DNA [6].
  • Several MEF2 co-repressors, such as Cabin1/Cain and class II histone deacetylases (HDACs), have been identified [7].
  • The myocyte enhancer factor-2 (MEF2) family of transcription factors has important roles in the development and function of T cells, neuronal cells and muscle cells [7].
  • Execution of the muscle differentiation program requires release of MEF2 from repression by HDACs, which are expressed constitutively in myoblasts and myotubes [8].

Chemical compound and disease context of MEF2A

  • Finally, Ang II increased protein synthesis, and this increase was inhibited by infection with an adenovirus construct that expresses the dominant-negative mutant of MEF2A but not by calcineurin inhibitors [9].

Biological context of MEF2A


Anatomical context of MEF2A


Associations of MEF2A with chemical compounds


Physical interactions of MEF2A

  • The MEF2 domain binds transcription factors MEF2A and MEF2D in vivo [12].
  • Furthermore, immunodepletion of the MEF2A-MEF2D complex from control extracts abolished binding to the MEF2 element [18].
  • Deletion of the GEF-binding domain (domain I) and the MEF2-binding domain prevented activation, strengthening the conclusion that promoter regulation occurs through these elements [12].
  • We report that HDAC4 and MITR contain calmodulin-binding domains that overlap with their MEF2-binding domains [21].
  • Here, we have characterized the complex between the MEF2-binding motif of class II HDACs and the MADS-box/MEF2S domain of MEF2B by structural and biochemical methods [22].

Enzymatic interactions of MEF2A

  • Threonines 312 and 319 within the transcription activation domain of MEF2A are the regulatory sites phosphorylated by p38 [23].
  • Taken together, these data demonstrate that, upon growth factor induction, BMK1 directly phosphorylates and activates three members of the MEF2 family of transcription factors thereby inducing MEF2-dependent gene expression [24].

Regulatory relationships of MEF2A

  • Consequently, we show that ICP0 is able to overcome the HDAC5 amino-terminal- and MITR-induced MEF2A repression in gene reporter assays [25].
  • Neither GEF nor MEF2A alone significantly activated GLUT4 promoter activity, but increased promoter activity 4- to 5-fold when expressed together [12].
  • In this study, we examined the potential role of the p38 MAP kinase pathway in regulating the other MEF2 family members [23].
  • The blocking of BMK1 signaling inhibits the epidermal growth factor-dependent activation of these three MEF2 transcription factors [24].
  • Supporting the physical interaction and deacetylase activity, HDAC3 repressed MEF2-dependent transcription and inhibited myogenesis [4].

Other interactions of MEF2A

  • These results identify MEF2A as a nuclear target for HDAC4-mediated repression and suggests that compartmentalization may be a novel mechanism for controlling the nuclear activity of this new family of deacetylases [11].
  • Here we show that HDAC7, a member of the class II histone deacetylases, specifically targets several members of myocyte enhancer factors, MEF2A, -2C, and -2D, and inhibits their transcriptional activity [26].
  • We have examined the interaction of PITX2 isoforms with myocyte-enhancing factor 2A (MEF2A), which is a known regulator of cardiac development [15].
  • A partially processed pseudogene (MEF2AP) corresponding to MEF2A was also isolated and characterized [27].
  • We have shown, by using transgenic mice, that the human GLUT4 promoter is regulated through the cooperative function of two distinct regulatory elements, domain 1 and the myocyte enhancer factor 2 (MEF2) domain [12].

Analytical, diagnostic and therapeutic context of MEF2A


  1. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor. De Luca, A., Severino, A., De Paolis, P., Cottone, G., De Luca, L., De Falco, M., Porcellini, A., Volpe, M., Condorelli, G. Biochem. J. (2003) [Pubmed]
  2. Molecular genetics of coronary artery disease. Wang, Q. Curr. Opin. Cardiol. (2005) [Pubmed]
  3. Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Wang, L., Fan, C., Topol, S.E., Topol, E.J., Wang, Q. Science (2003) [Pubmed]
  4. Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2. Grégoire, S., Xiao, L., Nie, J., Zhang, X., Xu, M., Li, J., Wong, J., Seto, E., Yang, X.J. Mol. Cell. Biol. (2007) [Pubmed]
  5. The MEF2B homologue differentially expressed in mouse embryonal carcinoma cells. Hidaka, K., Morisaki, T., Byun, S.H., Hashido, K., Toyama, K., Mukai, T. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  6. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Molkentin, J.D., Black, B.L., Martin, J.F., Olson, E.N. Cell (1995) [Pubmed]
  7. Sequence-specific recruitment of transcriptional co-repressor Cabin1 by myocyte enhancer factor-2. Han, A., Pan, F., Stroud, J.C., Youn, H.D., Liu, J.O., Chen, L. Nature (2003) [Pubmed]
  8. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. McKinsey, T.A., Zhang, C.L., Lu, J., Olson, E.N. Nature (2000) [Pubmed]
  9. Angiotensin II induces myocyte enhancer factor 2- and calcineurin/nuclear factor of activated T cell-dependent transcriptional activation in vascular myocytes. Suzuki, E., Nishimatsu, H., Satonaka, H., Walsh, K., Goto, A., Omata, M., Fujita, T., Nagai, R., Hirata, Y. Circ. Res. (2002) [Pubmed]
  10. Lack of MEF2A mutations in coronary artery disease. Weng, L., Kavaslar, N., Ustaszewska, A., Doelle, H., Schackwitz, W., Hébert, S., Cohen, J.C., McPherson, R., Pennacchio, L.A. J. Clin. Invest. (2005) [Pubmed]
  11. HDAC4 deacetylase associates with and represses the MEF2 transcription factor. Miska, E.A., Karlsson, C., Langley, E., Nielsen, S.J., Pines, J., Kouzarides, T. EMBO J. (1999) [Pubmed]
  12. Regulation of the human GLUT4 gene promoter: interaction between a transcriptional activator and myocyte enhancer factor 2A. Knight, J.B., Eyster, C.A., Griesel, B.A., Olson, A.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  13. p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple steps. Wu, Z., Woodring, P.J., Bhakta, K.S., Tamura, K., Wen, F., Feramisco, J.R., Karin, M., Wang, J.Y., Puri, P.L. Mol. Cell. Biol. (2000) [Pubmed]
  14. MEF2 protein expression, DNA binding specificity and complex composition, and transcriptional activity in muscle and non-muscle cells. Ornatsky, O.I., McDermott, J.C. J. Biol. Chem. (1996) [Pubmed]
  15. Cell-specific activation of the atrial natriuretic factor promoter by PITX2 and MEF2A. Toro, R., Saadi, I., Kuburas, A., Nemer, M., Russo, A.F. J. Biol. Chem. (2004) [Pubmed]
  16. The MEF2A and MEF2D isoforms are differentially regulated in muscle and adipose tissue during states of insulin deficiency. Mora, S., Yang, C., Ryder, J.W., Boeglin, D., Pessin, J.E. Endocrinology (2001) [Pubmed]
  17. Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity. Zhu, B., Gulick, T. Mol. Cell. Biol. (2004) [Pubmed]
  18. The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter. Mora, S., Pessin, J.E. J. Biol. Chem. (2000) [Pubmed]
  19. Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1. Al-Khalili, L., Forsgren, M., Kannisto, K., Zierath, J.R., Lönnqvist, F., Krook, A. Diabetologia (2005) [Pubmed]
  20. Post-translational control of the MEF2A transcriptional regulatory protein. Ornatsky, O.I., Cox, D.M., Tangirala, P., Andreucci, J.J., Quinn, Z.A., Wrana, J.L., Prywes, R., Yu, Y.T., McDermott, J.C. Nucleic Acids Res. (1999) [Pubmed]
  21. Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4. Youn, H.D., Grozinger, C.M., Liu, J.O. J. Biol. Chem. (2000) [Pubmed]
  22. Mechanism of recruitment of class II histone deacetylases by myocyte enhancer factor-2. Han, A., He, J., Wu, Y., Liu, J.O., Chen, L. J. Mol. Biol. (2005) [Pubmed]
  23. Regulation of the MEF2 family of transcription factors by p38. Zhao, M., New, L., Kravchenko, V.V., Kato, Y., Gram, H., di Padova, F., Olson, E.N., Ulevitch, R.J., Han, J. Mol. Cell. Biol. (1999) [Pubmed]
  24. Big mitogen-activated kinase regulates multiple members of the MEF2 protein family. Kato, Y., Zhao, M., Morikawa, A., Sugiyama, T., Chakravortty, D., Koide, N., Yoshida, T., Tapping, R.I., Yang, Y., Yokochi, T., Lee, J.D. J. Biol. Chem. (2000) [Pubmed]
  25. Functional interaction between class II histone deacetylases and ICP0 of herpes simplex virus type 1. Lomonte, P., Thomas, J., Texier, P., Caron, C., Khochbin, S., Epstein, A.L. J. Virol. (2004) [Pubmed]
  26. Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7. Kao, H.Y., Verdel, A., Tsai, C.C., Simon, C., Juguilon, H., Khochbin, S. J. Biol. Chem. (2001) [Pubmed]
  27. Structures and chromosome locations of the human MEF2A gene and a pseudogene MEF2AP. Suzuki, E., Lowry, J., Sonoda, G., Testa, J.R., Walsh, K. Cytogenet. Cell Genet. (1996) [Pubmed]
  28. Regional chromosomal assignments for four members of the MADS domain transcription enhancer factor 2 (MEF2) gene family to human chromosomes 15q26, 19p12, 5q14, and 1q12-q23. Hobson, G.M., Krahe, R., Garcia, E., Siciliano, M.J., Funanage, V.L. Genomics (1995) [Pubmed]
  29. Molecular cloning and developmental expression patterns of the MyoD and MEF2 families of muscle transcription factors in the carp. Kobiyama, A., Nihei, Y., Hirayama, Y., Kikuchi, K., Suetake, H., Johnston, I.A., Watabe, S. J. Exp. Biol. (1998) [Pubmed]
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