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Gene Review

MEF2D  -  myocyte enhancer factor 2D

Homo sapiens

Synonyms: Myocyte-specific enhancer factor 2D
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High impact information on MEF2D

  • HDAC7 inhibits the expression of Nur77, an orphan receptor involved in apoptosis and negative selection, via the transcription factor MEF2D [1].
  • It has been shown that nuclear factor of activated T cells (NFAT) interacts with MEF2D and enhances its transcriptional activity, offering a plausible mechanism of activation of MEF2D by calcineurin [2].
  • The MEF2 domain binds transcription factors MEF2A and MEF2D in vivo [3].
  • In contrast, HDAC3 efficiently deacetylated MEF2D in vitro and in vivo [4].
  • We report here that treatment of HEK293 cells with trichostatin A or nicotinamide upregulated MEF2D acetylation, suggesting that different deacetylases catalyze the deacetylation [4].

Biological context of MEF2D


Anatomical context of MEF2D


Physical interactions of MEF2D

  • Furthermore, immunodepletion of the MEF2A-MEF2D complex from control extracts abolished binding to the MEF2 element [14].

Regulatory relationships of MEF2D

  • These data strongly suggest that the MEF2A-MEF2D heterodimer is selectively decreased in insulin-deficient diabetes and is responsible for hormonally regulated expression of the GLUT4 gene [14].
  • Transient transfection experiments showed that co-expression of MEF2D and Sp1 synergistically activated the CD14 promoter [15].
  • Like its relatives, cloned hMEF2D is capable of activating transcription via sequence-specific binding to the MEF2 site, recapitulating endogenous tissue-specific MEF2 activity [8].
  • MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner [16].

Other interactions of MEF2D

  • These changes seemed to be correlated with the alternative splicing changes of MEF2 genes, especially MEF2D [6].
  • The sites phosphorylated by activated BMK1 were mapped to Ser-355, Thr-312, and Thr-319 of MEF2A and Ser-179 of MEF2D both in vitro and in vivo [17].
  • Transient co-expression of p300, MEF2D, NFATp and constitutively active calcineurin is sufficient to recapitulate TCR signaling for the selective induction of the endogenous Nur77 gene [2].
  • We also show that DAZAP1/MEF2D is a sequence-specific RNA-binding protein [9].
  • Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter [15].

Analytical, diagnostic and therapeutic context of MEF2D


  1. HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis. Dequiedt, F., Kasler, H., Fischle, W., Kiermer, V., Weinstein, M., Herndier, B.G., Verdin, E. Immunity (2003) [Pubmed]
  2. Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis. Youn, H.D., Chatila, T.A., Liu, J.O. EMBO J. (2000) [Pubmed]
  3. 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]
  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. Control of MEF2 transcriptional activity by coordinated phosphorylation and sumoylation. Grégoire, S., Tremblay, A.M., Xiao, L., Yang, Q., Ma, K., Nie, J., Mao, Z., Wu, Z., Giguère, V., Yang, X.J. J. Biol. Chem. (2006) [Pubmed]
  6. Expression of MEF2 genes during human cardiac development. Iida, K., Hidaka, K., Takeuchi, M., Nakayama, M., Yutani, C., Mukai, T., Morisaki, T. Tohoku J. Exp. Med. (1999) [Pubmed]
  7. 14-3-3tau associates with and activates the MEF2D transcription factor during muscle cell differentiation. Choi, S.J., Park, S.Y., Han, T.H. Nucleic Acids Res. (2001) [Pubmed]
  8. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Breitbart, R.E., Liang, C.S., Smoot, L.B., Laheru, D.A., Mahdavi, V., Nadal-Ginard, B. Development (1993) [Pubmed]
  9. Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia. Prima, V., Gore, L., Caires, A., Boomer, T., Yoshinari, M., Imaizumi, M., Varella-Garcia, M., Hunger, S.P. Leukemia (2005) [Pubmed]
  10. 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]
  11. Requirement of MEF2D in the induced differentiation of HL60 promyeloid cells. Shin, H.H., Seoh, J.Y., Chung, H.Y., Choi, S.J., Hahn, M.J., Kang, J.S., Choi, M.S., Han, T.H. Mol. Immunol. (1999) [Pubmed]
  12. Regulatory role of MEF2D in serum induction of the c-jun promoter. Han, T.H., Prywes, R. Mol. Cell. Biol. (1995) [Pubmed]
  13. 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]
  14. 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]
  15. Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter. Park, S.Y., Shin, H.M., Han, T.H. Mol. Immunol. (2002) [Pubmed]
  16. Menin represses JunD transcriptional activity in protein kinase C theta-mediated Nur77 expression. Kim, H., Lee, J.E., Kim, B.Y., Cho, E.J., Kim, S.T., Youn, H.D. Exp. Mol. Med. (2005) [Pubmed]
  17. 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]
  18. Development of a new epitope tag recognized by a monoclonal antibody to Rickettsia typhi. Lee, J.R., Chang, Y.Y., Hahn, M.J. BioTechniques (2001) [Pubmed]
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