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Gene Review

MEF2C  -  myocyte enhancer factor 2C

Homo sapiens

Synonyms: C5DELq14.3, DEL5q14.3, Myocyte-specific enhancer factor 2C
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Disease relevance of MEF2C

  • Our results thus indicate that MEF2C is a marker for hippocampal neurons that are resistant to ischemia [1].
  • In this study, the distribution of MEF2C expression in brain was studied in normal adult gerbils and in adult gerbils subjected to 10 min of global cerebral ischemia [1].
  • By co-transfection studies in P19 embryonal carcinoma cells, we demonstrated that MEF2C and GATA-4 each have an activating effect on the alphaT-catenin promoter [2].

High impact information on MEF2C

  • We found that in monocytic cells, LPS increases the transactivation activity of MEF2C through p38-catalysed phosphorylation [3].
  • One consequence of MEF2C activation is increased c-jun gene transcription [3].
  • We establish that calreticulin works upstream of calcineurin and MEF2C in a Ca(2+)-dependent signal transduction cascade that links the endoplasmic reticulum and the nucleus during cardiac development [4].
  • Our study illustrates the existence of a positive feedback mechanism that ensures an adequate supply of releasable Ca(2+) is maintained within the cell for activation of calcineurin and, subsequently, for proper functioning of MEF2C [4].
  • In mammals, the earliest site of MEF2 expression is the heart where the MEF2C isoform is detectable as early as embryonic day 7 [5].

Biological context of MEF2C


Anatomical context of MEF2C


Associations of MEF2C with chemical compounds

  • We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII) [13].
  • Mutagenesis of this serine to an aspartic acid resulted in an increase in DNA binding and transcriptional activity of MEF2C comparable to that observed when this site was phosphorylated, suggesting that phosphorylation augments DNA binding activity by introducing negative charge [13].
  • In these experiments we show that MEF2C protein and MEF2-binding sites are necessary for the p38 MAPK pathway to regulate the transcription of muscle creatine kinase reporter gene [14].
  • Only MEF2C regulated transcripts (glucose transporter 4, SERCA2a, and myosin heavy chain alpha) were lower in the diabetic group compared with the nondiabetic group [15].

Physical interactions of MEF2C

  • These results suggest that HDAC4 interacts with transcription factors such as MEF2C to negatively regulate gene expression [16].
  • We investigated the roles of the PPRE and the MEF2 binding sites and the potential interaction between PPARalpha and MEF2C regulating the CPT1beta gene promoter [17].
  • We show that a constitutively activated form of Notch specifically blocks DNA binding by MEF2C, as well as its ability to cooperate with MyoD and myogenin to activate myogenesis [18].
  • Two-hybrid assays and coimmunoprecipitations show that this region of MEF2C interacts directly with the ankyrin repeat region of Notch [18].

Regulatory relationships of MEF2C


Other interactions of MEF2C


Analytical, diagnostic and therapeutic context of MEF2C


  1. Myocyte-specific enhancer binding factor 2C expression in gerbil brain following global cerebral ischemia. Speliotes, E.K., Kowall, N.W., Shanti, B.F., Kosofsky, B., Finklestein, S.P., Leifer, D. Neuroscience (1996) [Pubmed]
  2. GATA-4 and MEF2C transcription factors control the tissue-specific expression of the alphaT-catenin gene CTNNA3. Vanpoucke, G., Goossens, S., De Craene, B., Gilbert, B., van Roy, F., Berx, G. Nucleic Acids Res. (2004) [Pubmed]
  3. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Han, J., Jiang, Y., Li, Z., Kravchenko, V.V., Ulevitch, R.J. Nature (1997) [Pubmed]
  4. Calreticulin signals upstream of calcineurin and MEF2C in a critical Ca(2+)-dependent signaling cascade. Lynch, J., Guo, L., Gelebart, P., Chilibeck, K., Xu, J., Molkentin, J.D., Agellon, L.B., Michalak, M. J. Cell Biol. (2005) [Pubmed]
  5. GATA-dependent recruitment of MEF2 proteins to target promoters. Morin, S., Charron, F., Robitaille, L., Nemer, M. EMBO J. (2000) [Pubmed]
  6. 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]
  7. Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity. Zhu, B., Gulick, T. Mol. Cell. Biol. (2004) [Pubmed]
  8. 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]
  9. 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]
  10. Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding activity, transcriptional activity, and myogenic differentiation. Ma, K., Chan, J.K., Zhu, G., Wu, Z. Mol. Cell. Biol. (2005) [Pubmed]
  11. SOX18 directly interacts with MEF2C in endothelial cells. Hosking, B.M., Wang, S.C., Chen, S.L., Penning, S., Koopman, P., Muscat, G.E. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. Characterization of myocyte enhancer factor 2 (MEF2) expression in B and T cells: MEF2C is a B cell-restricted transcription factor in lymphocytes. Swanson, B.J., Jäck, H.M., Lyons, G.E. Mol. Immunol. (1998) [Pubmed]
  13. Phosphorylation of the MADS-Box transcription factor MEF2C enhances its DNA binding activity. Molkentin, J.D., Li, L., Olson, E.N. J. Biol. Chem. (1996) [Pubmed]
  14. p38 mitogen-activated protein kinase pathway promotes skeletal muscle differentiation. Participation of the Mef2c transcription factor. Zetser, A., Gredinger, E., Bengal, E. J. Biol. Chem. (1999) [Pubmed]
  15. Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure. Razeghi, P., Young, M.E., Cockrill, T.C., Frazier, O.H., Taegtmeyer, H. Circulation (2002) [Pubmed]
  16. HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor. Wang, A.H., Bertos, N.R., Vezmar, M., Pelletier, N., Crosato, M., Heng, H.H., Th'ng, J., Han, J., Yang, X.J. Mol. Cell. Biol. (1999) [Pubmed]
  17. Functional interaction between peroxisome proliferator-activated receptors-alpha and Mef-2C on human carnitine palmitoyltransferase 1beta (CPT1beta) gene activation. Baldán, A., Relat, J., Marrero, P.F., Haro, D. Nucleic Acids Res. (2004) [Pubmed]
  18. Activated notch inhibits myogenic activity of the MADS-Box transcription factor myocyte enhancer factor 2C. Wilson-Rawls, J., Molkentin, J.D., Black, B.L., Olson, E.N. Mol. Cell. Biol. (1999) [Pubmed]
  19. 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]
  20. SMRTE inhibits MEF2C transcriptional activation by targeting HDAC4 and 5 to nuclear domains. Wu, X., Li, H., Park, E.J., Chen, J.D. J. Biol. Chem. (2001) [Pubmed]
  21. Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation. Okamoto, S., Krainc, D., Sherman, K., Lipton, S.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  22. Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors. Yang, S.H., Galanis, A., Sharrocks, A.D. Mol. Cell. Biol. (1999) [Pubmed]
  23. Caspase-dependent regulation of histone deacetylase 4 nuclear-cytoplasmic shuttling promotes apoptosis. Paroni, G., Mizzau, M., Henderson, C., Del Sal, G., Schneider, C., Brancolini, C. Mol. Biol. Cell (2004) [Pubmed]
  24. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. Kato, Y., Kravchenko, V.V., Tapping, R.I., Han, J., Ulevitch, R.J., Lee, J.D. EMBO J. (1997) [Pubmed]
  25. hMusTRD1alpha1 represses MEF2 activation of the troponin I slow enhancer. Polly, P., Haddadi, L.M., Issa, L.L., Subramaniam, N., Palmer, S.J., Tay, E.S., Hardeman, E.C. J. Biol. Chem. (2003) [Pubmed]
  26. Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1. Krainc, D., Bai, G., Okamoto, S., Carles, M., Kusiak, J.W., Brent, R.N., Lipton, S.A. J. Biol. Chem. (1998) [Pubmed]
  27. Myocyte-specific enhancer binding factor 2C expression in human brain development. Leifer, D., Golden, J., Kowall, N.W. Neuroscience (1994) [Pubmed]
  28. 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]
  29. Hybrid cardiomyocytes derived by cell fusion in heterotopic cardiac xenografts. Dedja, A., Zaglia, T., Dall'Olmo, L., Chioato, T., Thiene, G., Fabris, L., Ancona, E., Schiaffino, S., Ausoni, S., Cozzi, E. FASEB J. (2006) [Pubmed]
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