Gene Symbol: Mef2a
Description: myocyte enhancer factor 2a
Alias: myocyte-specific enhancer factor 2A
Species: rat
Products:     Mef2a

Top Publications

  1. Han T, Prywes R. Regulatory role of MEF2D in serum induction of the c-jun promoter. Mol Cell Biol. 1995;15:2907-15 pubmed
    ..MEF2 sites, found in many muscle-specific enhancers, are bound by a family of transcription factors, MEF2A through -D, which are related to serum response factor in their DNA binding domains...
  2. Lin X, Shah S, Bulleit R. The expression of MEF2 genes is implicated in CNS neuronal differentiation. Brain Res Mol Brain Res. 1996;42:307-16 pubmed
    ..In the developing postnatal cerebellum, RNA blot analysis revealed that MEF2A and MEF2D RNA levels increase after birth...
  3. Liu L, Cavanaugh J, Wang Y, Sakagami H, Mao Z, Xia Z. ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons. Proc Natl Acad Sci U S A. 2003;100:8532-7 pubmed
    ..These data suggest that ERK5 activation of myocyte enhancer factor 2-induced gene expression may play an important and novel role in the development of the CNS by mediating NT-promoted survival of embryonic neurons. ..
  4. Wang Y, Liu L, Xia Z. Brain-derived neurotrophic factor stimulates the transcriptional and neuroprotective activity of myocyte-enhancer factor 2C through an ERK1/2-RSK2 signaling cascade. J Neurochem. 2007;102:957-66 pubmed
    ..Together, our data identifies ERK1/2-RSK2 signaling as a novel mechanism by which neurotrophins activate MEF2C and promote neuronal survival. ..
  5. Aude Garcia C, Collin Faure V, Bausinger H, Hanau D, Rabilloud T, Lemercier C. Dual roles for MEF2A and MEF2D during human macrophage terminal differentiation and c-Jun expression. Biochem J. 2010;430:237-44 pubmed publisher
    ..We show in the present study that MEF2A and MEF2D, two other MEF2 family members, are expressed in human primary monocytes and in higher amounts in ..
  6. Naya F, Black B, Wu H, Bassel Duby R, Richardson J, Hill J, et al. Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat Med. 2002;8:1303-9 pubmed
    The four MEF2 transcription factors (MEF2A, -B, -C, and -D) regulate differentiation and calcium-dependent gene expression in muscle cells...
  7. Shalizi A, Gaudilliere B, Yuan Z, Stegmuller J, Shirogane T, Ge Q, et al. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science. 2006;311:1012-7 pubmed
    ..We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex...
  8. Flavell S, Cowan C, Kim T, Greer P, Lin Y, Paradis S, et al. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science. 2006;311:1008-12 pubmed
    ..These findings define an activity-dependent transcriptional program that may control synapse number during development. ..
  9. Li J, Vargas M, Kapiloff M, Dodge Kafka K. Regulation of MEF2 transcriptional activity by calcineurin/mAKAP complexes. Exp Cell Res. 2013;319:447-54 pubmed publisher
    ..Together these data illustrate the importance of calcineurin anchoring by the mAKAP scaffold for MEF2 regulation. ..

More Information


  1. Zhao M, New L, Kravchenko V, Kato Y, Gram H, Di Padova F, et al. Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol. 1999;19:21-30 pubmed
    ..We found that MEF2A, but not MEF2B or MEF2D, is a substrate for p38...
  2. Plessy C, Pascarella G, Bertin N, Akalin A, Carrieri C, Vassalli A, et al. Promoter architecture of mouse olfactory receptor genes. Genome Res. 2012;22:486-97 pubmed publisher
    ..OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters...
  3. Quinn Z, Yang C, Wrana J, McDermott J. Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res. 2001;29:732-42 pubmed
    ..We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays...
  4. Kobarg C, Kobarg J, Crosara Alberto D, Theizen T, Franchini K. MEF2C DNA-binding activity is inhibited through its interaction with the regulatory protein Ki-1/57. FEBS Lett. 2005;579:2615-22 pubmed
    ..Ki-1/57 also exerts an inhibitory effect upon MEF2C DNA binding activity. These results suggest that Ki-1/57 is a new interacting partner of MEF2 protein and may be involved in the regulation of MEF2 at the onset of hypertrophy. ..
  5. Phan N, Wang C, Lin Y. The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats. Toxicology. 2014;324:123-35 pubmed publisher
    ..Collectively, based on our real-time PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway.
  6. Silva J, Giannocco G, Furuya D, Lima G, Moraes P, Nachef S, et al. NF-kappaB, MEF2A, MEF2D and HIF1-a involvement on insulin- and contraction-induced regulation of GLUT4 gene expression in soleus muscle. Mol Cell Endocrinol. 2005;240:82-93 pubmed
    ..Differently, in vitro, muscle contraction led to a rapid increase (35-80%) in GLUT4, MEF2A, MEF2D and HIF1-a mRNAs...
  7. Komuro I, Schalling M, Jahn L, Bodmer R, Jenkins N, Copeland N, et al. Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter. EMBO J. 1993;12:1387-401 pubmed
    ..Although the true biological role of Gtx is not known, these results suggest that Gtx is a novel cell-type specific homeobox gene that has the potential to act as a transcriptional repressor for a subset of serum-inducible genes. ..
  8. Gray S, Feinberg M, Hull S, Kuo C, Watanabe M, Sen Banerjee S, et al. The Krüppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem. 2002;277:34322-8 pubmed
    ..00001) glucose uptake are increased in KLF15-overexpressing adipocytes. In co-transfection assays, KLF15 and MEF2A, a known activator of GLUT4, synergistically activates the GLUT4 promoter...
  9. Ewen E, Snyder C, Wilson M, Desjardins D, Naya F. The Mef2A transcription factor coordinately regulates a costamere gene program in cardiac muscle. J Biol Chem. 2011;286:29644-53 pubmed publisher
    ..Characterization of Mef2A knock-out mice has revealed severe myofibrillar defects in cardiac muscle indicating a requirement for Mef2A in ..
  10. Di Lisi R, Millino C, Calabria E, Altruda F, Schiaffino S, Ausoni S. Combinatorial cis-acting elements control tissue-specific activation of the cardiac troponin I gene in vitro and in vivo. J Biol Chem. 1998;273:25371-80 pubmed
    ..A mutation that blocks this binding markedly reduces gene activation in vivo and in vitro, and overexpression of MEF2A, MEF2C, and MEF2D in noncardiac cells transactivates the cardiac troponin I promoter...
  11. Finsterwald C, Carrard A, Martin J. Role of salt-inducible kinase 1 in the activation of MEF2-dependent transcription by BDNF. PLoS ONE. 2013;8:e54545 pubmed publisher
    ..Together, these data identify a previously unrecognized mechanism by which SIK1 mediates the activation of MEF2-dependent transcription by BDNF. ..
  12. Czubryt M, Lamoureux L, Ramjiawan A, Abrenica B, Jangamreddy J, Swan K. Regulation of cardiomyocyte Glut4 expression by ZAC1. J Biol Chem. 2010;285:16942-50 pubmed publisher
    ..This work identifies ZAC1 as a novel and previously unknown regulator of cardiomyocyte Glut4 expression and glucose uptake. Our results also implicate MEF2 as a regulator of ZAC1 expression in response to induction of hypertrophy. ..
  13. Fiore R, Khudayberdiev S, Christensen M, Siegel G, Flavell S, Kim T, et al. Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J. 2009;28:697-710 pubmed publisher
    ..In summary, we have described a novel regulatory pathway that couples activity-dependent transcription to miRNA-dependent translational control of gene expression during neuronal development. ..
  14. Durham J, Brand O, Arnold M, Reynolds J, Muthukumar L, Weiler H, et al. Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein. J Biol Chem. 2006;281:6841-9 pubmed
    ..Here, we describe the characterization of a direct, downstream target gene for the MEF2A transcription factor encoding a large, muscle-specific protein that localizes to the costamere in striated muscle...
  15. Desjardins C, Naya F. Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors. J Biol Chem. 2017;292:10613-10629 pubmed publisher
    ..Knockdown of individual MEF2 proteins, MEF2A, -C, and -D, in primary neonatal cardiomyocytes resulted in radically distinct and opposite effects on cellular ..
  16. Martorell Riera A, Segarra Mondejar M, Muñoz J, Ginet V, Olloquequi J, Pérez Clausell J, et al. Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. EMBO J. 2014;33:2388-407 pubmed publisher
    ..Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke. ..
  17. Shalizi A, Bilimoria P, Stegmuller J, Gaudilliere B, Yang Y, Shuai K, et al. PIASx is a MEF2 SUMO E3 ligase that promotes postsynaptic dendritic morphogenesis. J Neurosci. 2007;27:10037-46 pubmed
    ..Sumoylation of the transcription factor myocyte enhancer factor 2A (MEF2A) promotes the differentiation of postsynaptic granule neuron dendritic claws in the cerebellar cortex...
  18. Jung S, Ko Y. TRIM72, a novel negative feedback regulator of myogenesis, is transcriptionally activated by the synergism of MyoD (or myogenin) and MEF2. Biochem Biophys Res Commun. 2010;396:238-45 pubmed publisher
    ..Taken together all these data, we concluded that the synergism of MyoD (or myogenin) and MEF2 is necessary for TRIM72 expression during C2C12 differentiation. ..
  19. Barsyte Lovejoy D, Galanis A, Clancy A, Sharrocks A. ERK5 is targeted to myocyte enhancer factor 2A (MEF2A) through a MAPK docking motif. Biochem J. 2004;381:693-9 pubmed
    ..The presence of a docking domain promotes both phosphorylation of myocyte enhancer factor, MEF2A, in vitro and its activation in vivo by ERK5...
  20. Yamaguchi N, Takahashi N, Xu L, Smithies O, Meissner G. Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca release channel. J Clin Invest. 2007;117:1344-53 pubmed
    ..Taken together, the data indicate that impaired CaM inhibition of RyR2, associated with defective sarcoplasmic reticulum Ca(2+) release and altered gene expression, leads to cardiac hypertrophy and early death. ..
  21. Katoh Y, Molkentin J, Dave V, Olson E, Periasamy M. MEF2B is a component of a smooth muscle-specific complex that binds an A/T-rich element important for smooth muscle myosin heavy chain gene expression. J Biol Chem. 1998;273:1511-8 pubmed
    ..from smooth muscle nuclear extract reacts with MEF2B-specific antibody, but not with antibodies specific to MEF2A, MEF2C, or MEF2D, suggesting that only MEF2B protein binds to the A/T-rich element...
  22. Leupin O, Kramer I, Collette N, Loots G, Natt F, Kneissel M, et al. Control of the SOST bone enhancer by PTH using MEF2 transcription factors. J Bone Miner Res. 2007;22:1957-67 pubmed
    ..Finally, siRNA-mediated knockdown of MEF2A, C, and D suppressed endogenous SOST expression in UMR-106 osteoblast-like cells...
  23. Smith J, Collins M, Grobler L, Magee C, Ojuka E. Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo. Am J Physiol Endocrinol Metab. 2007;292:E413-20 pubmed
    ..that the exercise-induced increase in muscle GLUT4 is preceded by increased binding of myocyte enhancer factor 2A (MEF2A) to its cis-element on the Glut4 promoter...
  24. Choi J, Jang H, Kim H, Kim S, Cho E, Youn H. Histone demethylase LSD1 is required to induce skeletal muscle differentiation by regulating myogenic factors. Biochem Biophys Res Commun. 2010;401:327-32 pubmed publisher
    ..Altogether, the present study suggests a de-repression model and expands the understanding on the dynamic regulation of chromatin during myogenesis...
  25. Lemonnier M, Buckingham M. Characterization of a cardiac-specific enhancer, which directs {alpha}-cardiac actin gene transcription in the mouse adult heart. J Biol Chem. 2004;279:55651-8 pubmed
    ..This site binds myocyte enhancer factor (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts...
  26. Schlesinger J, Schueler M, Grunert M, Fischer J, Zhang Q, Krueger T, et al. The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs. PLoS Genet. 2011;7:e1001313 pubmed publisher
    ..biology study integrating mRNA profiles with DNA-binding events of key cardiac transcription factors (Gata4, Mef2a, Nkx2...
  27. Yamada T, Yang Y, Huang J, Coppola G, Geschwind D, Bonni A. Sumoylated MEF2A coordinately eliminates orphan presynaptic sites and promotes maturation of presynaptic boutons. J Neurosci. 2013;33:4726-40 pubmed publisher
    ..We report that knockdown of the transcription factor MEF2A in primary neurons and importantly in the rat cerebellar cortex in vivo robustly increases the density of orphan ..
  28. Ye J, Llorian M, Cardona M, Rongvaux A, Moubarak R, Comella J, et al. A pathway involving HDAC5, cFLIP and caspases regulates expression of the splicing regulator polypyrimidine tract binding protein in the heart. J Cell Sci. 2013;126:1682-91 pubmed publisher
  29. Speksnijder N, Christensen K, Didriksen M, de Kloet E, Datson N. Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context. J Mol Neurosci. 2012;48:209-18 pubmed publisher
    ..At the same time, GR influences MEF2 activity and DNA binding. These results give novel insight into the molecular interplay of GR and MEF2 in the control of genes important for neuronal plasticity. ..
  30. Mukwevho E, Kohn T, Lang D, Nyatia E, Smith J, Ojuka E. Caffeine induces hyperacetylation of histones at the MEF2 site on the Glut4 promoter and increases MEF2A binding to the site via a CaMK-dependent mechanism. Am J Physiol Endocrinol Metab. 2008;294:E582-8 pubmed publisher
    ..05) and increased the amount of MEF2A that was bound to this site approximately 2.2-fold (P < 0.05) 4 h posttreatment compared with controls...
  31. Lemercier C, Verdel A, Galloo B, Curtet S, Brocard M, Khochbin S. mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity. J Biol Chem. 2000;275:15594-9 pubmed
    ..We found that HDAC5 was able to interact in vivo and in vitro with MEF2A, a MADS box transcription factor, and to strongly inhibit its transcriptional activity...
  32. Iida K, Hidaka K, Takeuchi M, Nakayama M, Yutani C, Mukai T, et al. Expression of MEF2 genes during human cardiac development. Tohoku J Exp Med. 1999;187:15-23 pubmed
    ..Expression of all four MEF2 transcripts (MEF2A, MEF2B, MEF2C, and MEF2D) were detected in all developmental stage of the human heart, while Mef2b transcripts ..
  33. Joseph J, Ayeleso A, Mukwevho E. Exercise increases hyper-acetylation of histones on the Cis-element of NRF-1 binding to the Mef2a promoter: Implications on type 2 diabetes. Biochem Biophys Res Commun. 2017;486:83-87 pubmed publisher
    ..In type-2 diabetes, critical genes are down-regulated such as those involved in glucose transport (GLUT4, MEF2A) and also oxidative phosphorylation (NRF-1 and its target genes)...
  34. Clark A, Naya F. MicroRNAs in the Myocyte Enhancer Factor 2 (MEF2)-regulated Gtl2-Dio3 Noncoding RNA Locus Promote Cardiomyocyte Proliferation by Targeting the Transcriptional Coactivator Cited2. J Biol Chem. 2015;290:23162-72 pubmed publisher
    ..demonstrated previously that microRNAs encoded by the Gtl2-Dio3 noncoding RNA locus function downstream of the MEF2A transcription factor in skeletal muscle regeneration...
  35. Xu J, Gong N, Bodi I, Aronow B, Backx P, Molkentin J. Myocyte enhancer factors 2A and 2C induce dilated cardiomyopathy in transgenic mice. J Biol Chem. 2006;281:9152-62 pubmed
    ..Specifically, multiple transgenic mouse lines with cardiac-specific overexpression of MEF2A or MEF2C presented with cardiomyopathy at base line or were predisposed to more fulminant disease following ..
  36. Wang X, Tang X, Li M, Marshall J, Mao Z. Regulation of neuroprotective activity of myocyte-enhancer factor 2 by cAMP-protein kinase A signaling pathway in neuronal survival. J Biol Chem. 2005;280:16705-13 pubmed
    ..This study identifies the transcription factor MEF2 as a target of cAMP-PKA pathway and demonstrates that PKA phosphorylation of MEF2 is a key step in modulating its DNA binding activity and ability to promote neuronal survival. ..
  37. Dirkx E, Gladka M, Philippen L, Armand A, Kinet V, Leptidis S, et al. Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nat Cell Biol. 2013;15:1282-93 pubmed publisher
    ..Our results reveal that signalling cascades integrate with microRNAs to induce the expression of the bHLH transcription factor Hand2 in the postnatal mammalian myocardium with impact on embryonic gene programs in heart failure. ..
  38. Black B, Ligon K, Zhang Y, Olson E. Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family. J Biol Chem. 1996;271:26659-63 pubmed
    ..These results suggest that members of the MEF2 family perform similar roles in synergistic activation of transcription in myogenic and neurogenic lineages by serving as cofactors for cell type-specific bHLH proteins. ..
  39. Wang Q. Advances in the genetic basis of coronary artery disease. Curr Atheroscler Rep. 2005;7:235-41 pubmed
    ..One disease-causing gene for CAD and MI has been identified as MEF2A, which is located on chromosome 15q26...
  40. Huang K, Louis J, Donaldson L, Lim F, Sharrocks A, Clore G. Solution structure of the MEF2A-DNA complex: structural basis for the modulation of DNA bending and specificity by MADS-box transcription factors. EMBO J. 2000;19:2615-28 pubmed
    ..The solution structure of the 33 kDa complex between the dimeric DNA-binding core domain of the transcription factor MEF2A (residues 1-85) and a 20mer DNA oligonucleotide comprising the consensus sequence CTA(A/T)(4)TAG has been solved ..
  41. Morin S, Pozzulo G, Robitaille L, Cross J, Nemer M. MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. J Biol Chem. 2005;280:32272-8 pubmed
    ..These findings identify a novel mechanism for HAND action in the heart and provide a general paradigm to understand the mechanism of HAND action in organogenesis. ..
  42. Mao Z, Wiedmann M. Calcineurin enhances MEF2 DNA binding activity in calcium-dependent survival of cerebellar granule neurons. J Biol Chem. 1999;274:31102-7 pubmed
    ..In cultured primary cerebellar granule neurons, the electrophoretic mobility of MEF2A protein was sensitive to the level of extracellular potassium chloride (KCl) and depolarizing concentrations of ..
  43. Satoh K, Ohnishi J, Sato A, Takeyama M, Iemura S, Natsume T, et al. Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior formation in Xenopus development. Mol Cell Biol. 2007;27:7623-30 pubmed
    ..In the present study, we identified the transcription factor myocyte enhancer factor 2A (MEF2A) as a novel substrate for NLK...
  44. Feng B, Chen S, Chiu J, George B, Chakrabarti S. Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level. Am J Physiol Endocrinol Metab. 2008;294:E1119-26 pubmed publisher
    ..Cardiomyocytes were analyzed with respect to their size. mRNA expression of p300, MEF2A, MEF2C, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), angiotensinogen (ANG), cAMP-..
  45. Neely M, Robert E, Baucum A, Colbran R, Muly E, Deutch A. Localization of myocyte enhancer factor 2 in the rodent forebrain: regionally-specific cytoplasmic expression of MEF2A. Brain Res. 2009;1274:55-65 pubmed publisher
    ..We have analyzed the regional, cellular, and subcellular expression of MEF2A and MEF2D in the rodent brain...
  46. Toro R, Saadi I, Kuburas A, Nemer M, Russo A. Cell-specific activation of the atrial natriuretic factor promoter by PITX2 and MEF2A. J Biol Chem. 2004;279:52087-94 pubmed
    ..We have examined the interaction of PITX2 isoforms with myocyte-enhancing factor 2A (MEF2A), which is a known regulator of cardiac development...
  47. Liu X, Jin E, Zhi J, Li X. Identification of HZF1 as a novel target gene of the MEF2 transcription factor. Mol Med Rep. 2011;4:465-9 pubmed publisher
    The MADS box-containing transcription factors MEF2A-D regulate the expression of most skeletal and cardiac muscle structural genes...