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Gene Review

MYEF2  -  myelin expression factor 2

Homo sapiens

Synonyms: FLJ11213, HsT18564, KIAA1341, MEF-2, MST156, ...
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Disease relevance of MYEF2

  • We also discuss recent evidence that the myocyte enhancer factor 2 (MEF2) transcription factor family, which previously has been shown to be important in cardiac development and hypertrophy, may have a role in regulation of cardiac energy metabolism [1].
  • Balancing contractility and energy production: the role of myocyte enhancer factor 2 (MEF2) in cardiac hypertrophy [1].
  • The 5'-upstream sequence of pwsi18 contained putative cis-acting elements, namely an ABA-responsive element (ABRE), three G-boxes, three E-boxes, a MEF-2 sequence, four direct and two inverted repeats, and four sequences similar to DRE, which is involved in the dehydration response of Arabidopsis genes [2].
  • The nuclei in all sarcoma cells stained definitively positive for the transcription factor MEF-2 [3].
  • Electron microscopy and immunohistochemistry studies of pulmonary carcinosarcomas expressing the transcription factor MEF-2 and showing significant cell-to-cell, cell-to-matrix, and epithelial-mesenchymal interactions [3].

High impact information on MYEF2


Biological context of MYEF2

  • Oligomers corresponding to the region of the mlc-1/3 enhancer, which encompasses this conserved sequence, bound MEF-2 and competed for its binding to the mck enhancer [7].
  • The ability of MEF-2 to recognize conserved activating elements associated with multiple-specific genes suggests that this factor may participate in the coordinate regulation of genes during myogenesis [7].
  • In skeletal muscle cells, MEF-2 proteins interact with members of the MyoD family of transcriptional activators to synergistically activate gene expression [8].
  • SL-1 protein recognizes the consensus DNA sequence CTA(A/T)4TAR in vitro and can bind to the same regulatory sites as other A/T-rich sequence-specific binding activities, such as the muscle-specific regulatory factor, MEF-2 [9].
  • MEF-2C binds the MEF-2 site with high affinity and can activate transcription of a reporter gene linked to tandem copies of that site [10].

Anatomical context of MYEF2

  • MEF-2 was first detectable within 2 h after exposure of myoblasts to mitogen-deficient medium and increased in abundance for 24 to 48 h thereafter [7].
  • While the regulation of COXVIa (H) gene involves factors binding to both MEF2 and E box in a skeletal muscle-specific fashion, the COXVIII (H) gene is regulated by factors binding to two tandomly duplicated E boxes in both skeletal and cardiac myocytes [11].
  • Thus, the cardiogenic commitment and differentiation of the precardiac mesoderm, as exemplified by the appearance of cardiac MEF-2, MLC2, and alpha-actin gene products, occur earlier than previously thought and appear to be closely linked [12].
  • Except for mef2, the expression of these genes is largely restricted to the endodermal layer, the gastrodermis. mef2 is restricted to the ectoderm [13].
  • Functional synergism among the MyoD, MEF2, and Mt sites in myotubes has been demonstrated [14].

Associations of MYEF2 with chemical compounds

  • This myocyte-specific enhancer-binding factor, designated MEF-2, was undetectable in nuclear extracts from C2 or BC3H1 myoblasts or several nonmyogenic cell lines [7].
  • A 10-bp sequence, which was shown by DNase I footprinting and diethyl pyrocarbonate interference to interact directly with MEF-2, was identified within the rat and human mck enhancers, the rat myosin light-chain (mlc)-1/3 enhancer, and the chicken cardiac mlc-2A promoter [7].
  • The myocyte-specific enhancer-binding factor MEF-2 is a nuclear factor that interacts with a conserved element in the muscle creatine kinase and myosin light-chain 1/3 enhancers (L. A. Gossett, D. J. Kelvin, E. A. Sternberg, and E. N. Olson, Mol. Cell. Biol. 9:5022-5033, 1989) [15].
  • These include an E-box, a MEF2 element, and two other elements, USE B1 and USE C1 [16].
  • Murine embryonic fibroblasts (MEF) that are LRP-deficient due to targeted gene disruption and exotoxin selection (MEF-2), heterozygous fibroblasts (PEA-10), and wild-type fibroblasts (MEF-1) were compared [17].

Other interactions of MYEF2


Analytical, diagnostic and therapeutic context of MYEF2

  • Gel mobility shift assays, competition analysis, DNase I footprinting, and mutagenesis studies indicated that this element interacts through an A/T-rich box with a MEF-2 protein(s) and through a G-rich box with a novel ubiquitous factor(s) [19].
  • Mutations that eliminate PDP1 binding eliminate muscle activator function and severely reduce expression of a muscle activator plus MEF2 mini-enhancer [20].
  • The core enhancer region was delimited to a 195 bp Spe I- Acc I fragment and sequence analysis identified three MEF-1/E box and two MEF-2/AT-rich motifs as potential muscle-specific regulatory domains [21].
  • To address these issues, we have utilized a method coupling chromatin immunoprecipitation and CpG microarrays to characterize the genes associated with MEF2 in differentiating C(2)C(12) cells [22].


  1. Balancing contractility and energy production: the role of myocyte enhancer factor 2 (MEF2) in cardiac hypertrophy. Czubryt, M.P., Olson, E.N. Recent Prog. Horm. Res. (2004) [Pubmed]
  2. Isolation and characterization of a water stress-specific genomic gene, pwsi 18, from rice. Joshee, N., Kisaka, H., Kitagawa, Y. Plant Cell Physiol. (1998) [Pubmed]
  3. Electron microscopy and immunohistochemistry studies of pulmonary carcinosarcomas expressing the transcription factor MEF-2 and showing significant cell-to-cell, cell-to-matrix, and epithelial-mesenchymal interactions. Yamazaki, K. Virchows Arch. (2004) [Pubmed]
  4. Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Black, B.L., Olson, E.N. Annu. Rev. Cell Dev. Biol. (1998) [Pubmed]
  5. MEF2: a calcium-dependent regulator of cell division, differentiation and death. McKinsey, T.A., Zhang, C.L., Olson, E.N. Trends Biochem. Sci. (2002) [Pubmed]
  6. Identification of a novel first exon in the human dystrophin gene and of a new promoter located more than 500 kb upstream of the nearest known promoter. Nishio, H., Takeshima, Y., Narita, N., Yanagawa, H., Suzuki, Y., Ishikawa, Y., Ishikawa, Y., Minami, R., Nakamura, H., Matsuo, M. J. Clin. Invest. (1994) [Pubmed]
  7. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Gossett, L.A., Kelvin, D.J., Sternberg, E.A., Olson, E.N. Mol. Cell. Biol. (1989) [Pubmed]
  8. MEF-2 function is modified by a novel co-repressor, MITR. Sparrow, D.B., Miska, E.A., Langley, E., Reynaud-Deonauth, S., Kotecha, S., Towers, N., Spohr, G., Kouzarides, T., Mohun, T.J. EMBO J. (1999) [Pubmed]
  9. Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis. Chambers, A.E., Kotecha, S., Towers, N., Mohun, T.J. EMBO J. (1992) [Pubmed]
  10. Myocyte enhancer factor (MEF) 2C: a tissue-restricted member of the MEF-2 family of transcription factors. Martin, J.F., Schwarz, J.J., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  11. Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Lenka, N., Vijayasarathy, C., Mullick, J., Avadhani, N.G. Prog. Nucleic Acid Res. Mol. Biol. (1998) [Pubmed]
  12. Differential expression of the myocyte enhancer factor 2 family of transcription factors in development: the cardiac factor BBF-1 is an early marker for cardiogenesis. Goswami, S., Qasba, P., Ghatpande, S., Carleton, S., Deshpande, A.K., Baig, M., Siddiqui, M.A. Mol. Cell. Biol. (1994) [Pubmed]
  13. Investigating the origins of triploblasty: 'mesodermal' gene expression in a diploblastic animal, the sea anemone Nematostella vectensis (phylum, Cnidaria; class, Anthozoa). Martindale, M.Q., Pang, K., Finnerty, J.R. Development (2004) [Pubmed]
  14. A novel site, Mt, in the human desmin enhancer is necessary for maximal expression in skeletal muscle. Gao, J., Li, Z., Paulin, D. J. Biol. Chem. (1998) [Pubmed]
  15. Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products. Cserjesi, P., Olson, E.N. Mol. Cell. Biol. (1991) [Pubmed]
  16. Identification of a novel slow-muscle-fiber enhancer binding protein, MusTRD1. O'Mahoney, J.V., Guven, K.L., Lin, J., Joya, J.E., Robinson, C.S., Wade, R.P., Hardeman, E.C. Mol. Cell. Biol. (1998) [Pubmed]
  17. Embryonic fibroblasts that are genetically deficient in low density lipoprotein receptor-related protein demonstrate increased activity of the urokinase receptor system and accelerated migration on vitronectin. Weaver, A.M., Hussaini, I.M., Mazar, A., Henkin, J., Gonias, S.L. J. Biol. Chem. (1997) [Pubmed]
  18. The human skeletal alpha-actin gene is regulated by a muscle-specific enhancer that binds three nuclear factors. Muscat, G.E., Perry, S., Prentice, H., Kedes, L. Gene Expr. (1992) [Pubmed]
  19. Transcription of the human beta enolase gene (ENO-3) is regulated by an intronic muscle-specific enhancer that binds myocyte-specific enhancer factor 2 proteins and ubiquitous G-rich-box binding factors. Feo, S., Antona, V., Barbieri, G., Passantino, R., Calì, L., Giallongo, A. Mol. Cell. Biol. (1995) [Pubmed]
  20. PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes. Lin, S.C., Lin, M.H., Horváth, P., Reddy, K.L., Storti, R.V. Development (1997) [Pubmed]
  21. A muscle-specific enhancer within intron 1 of the human dystrophin gene is functionally dependent on single MEF-1/E box and MEF-2/AT-rich sequence motifs. Klamut, H.J., Bosnoyan-Collins, L.O., Worton, R.G., Ray, P.N. Nucleic Acids Res. (1997) [Pubmed]
  22. Identification of MEF2-regulated genes during muscle differentiation. Paris, J., Virtanen, C., Lu, Z., Takahashi, M. Physiol. Genomics (2004) [Pubmed]
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