Abstract
The MEF2 (myocyte enhancer factor 2) family of transcription factors is composed of four distinct vertebrate genes. These factors were first identified in muscle but are also present in brain. MEF2 is involved in neuronal survival and is able to regulate the growth and pruning of neurons in response to stimulation. Dendrite remodelling is under the control of genes that MEF2 can turn on or off and some of its target genes have been identified. Among them are immediate-early genes such as C-JUN and NUR77 and neuronal-activity-regulated genes such as ARC, SYNGAP, HOMER1A and BDNF. MEF2 is able to control the synapse number in the hippocampus in which its activation inhibits the growth of dendritic spines, highlighting its important role in memory and learning. In addition, mutations in the MEF2 gene has been found in patients with Rett-like disorder. MEF2 has also been implicated in other pathologies such as Alzheimer’s and Parkinson’s diseases.
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Abraham WC (2008) Metaplasticity: tuning synapses and networks for plasticity. Nat Rev Neurosci 9:387–399
Akhtar MW, Kim M-S, Adachi M, Morris MJ, Qi X, Richardson JA, Bassel-Duby, Olson EN, Kavalali ET, Monteggia LM (2012) In vivo analysis of mEF2 transcription factors in synapse regulation and neuronal survival. PLoS One 7:e34863
Andres V, Cervera M, Mahdavi V (1995) Determination of the consensus binding site for MEF2 expressed in muscle and brain reveals tissue-specific sequence constraints. J Biol Chem 270:23246–23249
Armani R, Archer H, Clarke A, Vasudevan P, Zweier C, Ho G, Williamson S, Cloosterman D, Yang N, Christodoulou J (2012) Transcription factor 4 and myocyte enhancer factor 2C mutations are not common causes of Rett syndrome. Am J Med Genet 158A:713–719
Barbosa AC, Kim MS, Ertunc M, Adachi M, Nelson ED, McAnally J, Richardson JA, Kavalali ET, Monteggia LM, Bassel-Duby R, Olson EN (2008) MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function. Proc Natl Acad Sci USA 105:9391–9396
Black BL, Olson EN (1998) Transcriptional control of muscle development by myocyte enhancer factor 2 (MEF) proteins. Annu Rev Cell Dev Biol 18:67–76
Blaeser F, Ho N, Prywes R, Chatila TA (2000) Ca(2+)-dependent gene expression mediated by MEF2 transcription factors. J Biol Chem 275:197–209
Burton TR, Dibrov A, Kashour T, Amara FM (2002) Anti-apoptotic wild-type Alzheimer amyloid precursor protein signalling involves the p38 mitogen-activated protein kinase/MEF2 pathway. Brain Res Mol Brain Res 108:102–120
Carouge D, Host L, Aunis D, Zwiller J, Anglard P (2010) CDKL5 is a brain MECP2 target gene regulated by DNA methylation. Neurobiol Dis 38:414–424
Cavanaugh JE, Ham J, Hetman M, Poser S, Yan C, Xia Z (2001) Differential regulation of mitogen-activated protein kinases ERK1/2 and ERK5 by neurotrophins, neuronal activity, and cAMP in neurons. J Neurosci 21:434–443
Chahrour M, Jung SY, Shaw C, Zhou X, Wong STC, Qin J, Zoghbi HY (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224–1228
Chen SX, Cherry A, Tari PK, Podgorski K, Kwong YKK, Haas K (2012) The transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity. Cell 151:41–55
Cole CJ, Mercaldo V, Restivo L, Yiu AP, Sekeres MJ, Han J-H, Vetere G, Pekar T, Ross PJ, Neve RL, Frankland PW, Josselyn SA (2012) MEF2 negatively regulates learning-induced structural plasticity and memory formation. Nat Neurosci 15:1255–1264
Dickey CA, de Mesquita DD, Morgan D, Pennypacker KR (2004) Induction of memory-associated immediate early genes by nerve growth factor in rat primary cortical neurons and differentiated mouse Neuro2A cells. Neurosci Lett 366:10–14
Dietrich JB, Takemori H, Grosch-Dirrig S, Bertorello A, Zwiller J (2012) Cocaine induces the expression of MEF2C transcription factor in rat striatum through the activation of SIK1 and phosphorylation of the histone deacetylase HDAC5. Synapse 66:61–70
Dong J, Canfield JM, Mehta AK, Shokes JE, Tian B, Childers WS, Simmons JA, Mao Z, Scott RA, Warncke K, Lynn DG (2007) Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity. Proc Natl Acad Sci USA 104:13313–13318
Dorval V, Fraser PE (2007) SUMO on the road to neurodegeneration. Biochem Biophys Acta 1773:694–706
Dron M, Meritet JF, Dandoy-Dron F, Meyniel J-P, Maury C, Tovey MG (2002) Molecular cloning of ADIR, a novel interferon responsive gene encoding a protein related to the torsins. Genomics 79:315–325
Escher P, Schorderet DF, Cottet S (2011) Altered expression of the transcription factor Mef2c during retinal degeneration in Rpe65−/− mice. Invest Ophtalmol Vis Sci 52:5933–5940
Flavell SW, Greenberg ME (2008) Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annu Rev Neurosci 31:563–590
Flavell SW, Cowan CW, Kim TK, Greer PK, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311:1008–1012
Flavell SW, Kim TK, Gray JM, Harmin DA, Hemberg M, Hong EJ, Markenscoff-Papadimitriou E, Bear DM, Greenberg ME (2008) Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron 60:1022–1038
Fleischmann A, Hvalby O, Jensen V, Strekalova T, Zacher C, Layer LE, Kvello A, Reschke M, Spanagel R, Sprengel R, Wagner EF, Gass P (2003) Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J Neurosci 23:9116–9122
Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792–1795
Fuzakawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38:447–460
Gao C, Negash S, Wang HS, Ledee D, Guo H, Russell P, Zelenka P (2001) Cdk5 mediates change in morphology and promotes apoptosis of astrocytoma cells in response to heat-shock. J Cell Sci 114:1145–1153
Gaudillière B, Konishi Y, de la Iglesia N, Yao G, Bonni A (2004) A CamKII-NeuroD signaling pathway specifies dendritic morphogenesis. Neuron 41:229–241
Gong X, Tang X, Wiedman M, Wang X, Peng J, Zheng D, Blair LA, Marshall J, Mao Z (2003) Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Neuron 38:33–46
Gocke C, Yu H, Kang J (2004) Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates. J Biol Chem 280:5004–5012
Gordon JW, Pagiatakis C, Salma J, Du M, Andreucci JJ, Zhao J, Hou G, Perry RL, Dan Q, Courtman D, Bendeck MP, McDermott JC (2009) Protein kinase A-regulated assembly of MEF2.HDAC4 repressor complex controls c-Jun expression in vascular smooth muscle cells. J Biol Chem 284:19027–19042
Grégoire S, Yang XJ (2005) Association with class IIa histone deacetylases upregulates the sumoylation of MEF2 transcription factors. Mol Cell Biol 25:8456–8464
Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA (2000) Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J Neurosci 20:3993–4001
Guzowski JF, Setlow B, Wagner EK, McGaugh JL (2001a) Experience-dependent gene expression in the rat hippocampus after spatial learning: a comparison of immediate–early genes Arc, c-fos, and zif268. J Neurosci 21:5089–5098
Guzowski JF, McNaughton BL, Barnes BA, Worley PF (2001b) Imaging neural activity with temporal and cellular resolution using FISH. Curr Opin Neurobiol 11:579–584
Hakim NHA, Kounishi T, Alam AHMK, Tsukahara T, Suzuki H (2010) Alternative splicing of Mef2c promoted by Fox-1 during neural differentiation in P19 cells. Genes Cells 15:255–267
Hetman M, Cavanaugh J, Kimelman D, Xia Z (2000) Role of glycogen synthase kinase-3beta in neuronal apoptosis induced by trophic withdrawal. J Neurosci 20:2567–2574
Hiroi N, Brown JR, Haile CN, Ye H, Greenberg ME, Nestler EJ (1997) FosB mutant mice: loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine’s psychomotor and rewarding effects. Proc Natl Acad Sci USA 94:10397–10402
Holloway CM, McIntyre C (2011) Post-training disruption of Arc protein expression in the anterior cingulate cortex impairs long-term memory for inhibitory avoidance training. Neurobiol Learning Memory 95:425–432
Johnson ES (2004) Protein modification by SUMO. Annu Rev Biochem 73:355–382
Jones MW, Errington ML, French PJ, Fine A, Bliss TV, Garel S, Charnay P, Bozon B, Laroche S, Davis S (2001) A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci 4:289–296
Kang J, Gocke CB, Yu H (2006) Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity. BMC Biochem 7:5
Kang SA, Na H, Kang HJ, Kim SH, Lee MH, Lee MO (2010) Regulation of Nur77 protein turnover through acetylation and deacetylation induced by p3000 and HDAC1. Biochem Pharmacol 80:867–873
Kato Y, Zhao M, Morikawa A, Sugiyama T, Chakravorty D, Koine N, Yoshida T, Tapping RI, Yang Y, Yokochi T, Lee JD (2000) Big mitogen-activated kinase regulates multiple members of the MEF2 protein family. J Biol Chem 275:18534–18540
Kim M-K, Kim S-C, Kang J-I, Hyun J-H, Boo H-J, Eun S-Y, Park D-B, Yoo E-S, Kang H-K, Kang J-H (2011) 6-Hydroxydopamine-induced PC12 cell death is mediated by MEF2D down-regulation. Neurochem Res 36:223–231
Ko J, Humbert S, Bronson RT, Takahashi S, Kulkarni AB, Li E, Tsai LH (2001) p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci 21:6758–6771
Korb E, Finkbeiner S (2011) Arc in synaptic plasticity: from gene to behaviour. Trends Neurosci 34:591–598
Kraytor MD, Orr HT (2002) The GSK3 beta signalling cascade and neurodegenerative disease. Curr Opin Neurobiol 12:275–278
Kumar V, Fahey PG, Jong YI, Ramanan N, O’Malley KL (2012) Activation of intracellular metabotropic glutamate receptor 5 in striatal neurons leads to up-regulation of genes associated with sustained synaptic transmission including Arc/Arg3.1 protein. J Biol Chem 287:5412–5425
Lahiri DK, Ge YW, Rogers JT, Sambamurti K, Greig NH, Maloney B (2006) Taking down the unindicated co-conspirators of amyloid beta-peptide-mediated neuronal death: shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factors. Curr Alzheimer Res 3:475–483
Lambert L, Bienvenu T, Allo L, Valduga M, Echenne B, Diebold B, Mignot C, Roth V, Saunier A, Moustaïne A, Jonveaux P, Philippe C (2012) MEF2C mutations are a rare cause of Rett or severe Rett-like encephalopathies. Clin Gen 82:499–501
Lazaro JB, Bailey PJ, Lassar AB (2002) Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation. Genes Dev 16:1792–1805
Lee PR, Cohen JE, Becker KG, Fields RD (2005) Gene expression in the conversion of early-phase to late-phase long-term potentiation. Ann N Y Acad Sci 555:115–121
Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA (1993) MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex. Proc Natl Acad Sci USA 90:1546–1550
Leifer D, Golden J, Kowall NW (1994) Myocyte-specific enhancer factor 2C expression in brain development. Neuroscience 63:1067–1079
Leysen I, Van der Gucht E, Eysel UT, Huybrechts R, Vandesande F, Arckens L (2004) Time-dependent changes in the expression of the MEF2 transcription factor family during topographic map reorganization in mammalian visual cortex. Eur J Neurosci 20:769–780
Li H, Radford JC, Ragusa MJ, Shea KL, McKercher SR, Zaremba JD, Soussou W, Nie Z, Kang Y-J, Okamoto S, Roberts AJ, Schwarz JJ, Lipton SA (2008) Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo. Proc Natl Acad Sci USA 105:9397–9402
Li L, Yun SH, Keblesh J, Trommer BL, Xiong H, Radulovic J, Tourtellotte WG (2007) Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. Mol Cell Neurosci 35:76–88
Li M, Linseman DA, Allen MP, Meintzer MK, Wang X, Laessig T, Wierman ME, Heidenreich KA (2001) Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase-mediated degradation during apoptosis of rat cerebellar granule neurons. J Neurosci 21:6544–6552
Li Z, McKercher SR, Cui J, Nie Z, Soussou W, Roberts AJ, Sallmen T, Lipton JH, Talantova M, Okamoto S, Lipton SA (2008) Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cells. J Neurosci 28:6557–6568
Lin X, Shah S, Bulleit RF (1996) The expression of MEF2 genes is implicated in CNS neuronal differentiation. Mol Brain Res 42:307–316
Linseman DA, Bartley CM, Le SS, Laessig TA, Bouchard RJ, Meintzer MK, Li M, Heidenreich KA (2003) inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca(2+)//calmodulin-dependent kinase II promotes depolarization-mediated cerebellar granule neuron survival. J Biol Chem 278:41472–41481
Liu L, Cavanaugh JE, Wang Y, Sakagami H, Mao Z, Xia Z (2003) 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 USA 100:8352–8537
Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J (2001) Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J 20:27–39
Lyons GE, Micales BK, Schwarz J, Martin JF, Olson EN (1995) Expression of the mef2 genes in the mouse central nervous system suggests a role in neuronal maturation. J Neurosci 15:5727–5738
Lyons MR, Schwarz CM, West AE (2012) Members of the myocyte enhancer factor 2 transcription factor family differentially regulate bdnf transcription in response to neuronal depolarization. J Neurosci 32:12780–12785
Mahanty NK, Sah P (1998) Calcium-permeable AMPA receptors mediate long-term poptentiation in interneurons in the amygdala. Nature 394:683–687
Mao Z, Bonni A, Xia F, Nadal-Vicens M, Greenberg ME (1999) Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science 286:785–790
Mari F, Azimonti S, Bertani I, Bolognese F, Colmobo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zapella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N (2005) CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early–onset seizure variant of Rett syndrome. Hum Mol Genet 14:1935–1946
Martin JF, Miano JM, Hustad CM, Copeland GM, Jenkins NA, Olson EN (1994) A Mef gene that generates a muscle-specific isoform via alternative mRNA splicing. Mol Cell Biol 14:1647–1656
Maxwell MA, Muscat GE (2006) The NR4A subgroup: immediate early response genes with pleiotropic physiological roles. Nucl Recept Signal 4:e002
McKinsey TA, Zhang CL, Olson EN (2001) Control of muscle development by dueling HATs and HDACs. Curr Opin Genet Dev 11:497–504
McKinsey TA, Zhang CL, Olson EN (2002) MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem Sci 27:40–47
Menzies FM, Hourez R, Imarisio S, Raspe M, Sadiq O, Chandraratna D, O’Kane C, Rock KL, Reits E, Goldberg AL, Rubinsztein DC (2010) Puromycin-sensitive aminopeptidase protects against aggregation-prone proteins via autophagy. Hum Mol Genet 19:4537–4586
Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T (1999) HDAC4 deacetylase associates with and represses the MEF2 transcription factor. EMBO J 18:5099–5107
Molkentin JD, Olson EN (1996) Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. Proc Natl Acad Sci USA 93:9366–9373
Molkentin JD, Black BL, Martin JF, Olson EN (1995) Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell 83:1125–1136
Mora A, Sabio G, Gonzalez-Polo RA, Cuenda A, Alessi DR, Alonso JC, Fuentes JM, Soler G, Centeno F (2001) Lithium inhibits caspase 3 activation and dephosphorylation of PKB and GSK3 induced by K+ deprivation in cerebellar granule cells. J Neurochem 78:199–206
Mori T, Wada T, Suzuki T, Kubota Y, Inagaki N (2007) Singar1, a novel RUN domain-containing protein, suppresses formation of surplus axons for neuronal polarity. J Biol Chem 282:19884–19893
Morin S, Charron F, Robitaille L, Nemer M (2000) GATA-dependent recruitment of MEF2 proteins to target promoters. EMBO J 19:2046–2055
Morrow EM, Yoo S-Y, Flavell SW, Kim T-K, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321:218–223
Nurrish SJ, Treismann R (1995) DNA binding specificity determinants in MADS-box transcription factors. Mol Cell Biol 15:4076–4085
Okamoto S, Krainc D, Sherman K, Lipton SA (2000) Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation. Proc Natl Acad Sci USA 97:7561–7566
Pfeiffer BE, Zang T, Wilkerson JR, Taniguchi M, Maksimova MA, Smith LN, Cowan CW, Huber KM (2010) Fragile X mental retardation protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron 66:191–197
Plath N, Ohana O, Dammermann B, Errington ML, Schmitz D, Gross C, Mao X, Engelsberg A, Mahlke C, Welzl H, Kobalz U, Stawrakakis A, Fernandez E, Waltereit R, Bick-Sander A, Therstappen E, Cooke SF, Blanquet V, Wurst W, Salmen B, Bösl MR, Lipp HP, Grant SG, Bliss TV, Wolfer DP, Kuhl D (2006) Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron 52:437–444
Pollock R, Treismann R (1991) Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev 5:2327–2341
Potthoff MJ, Olson EN (2007) MEF2: a central regulator of diverse developmental programs. Development 134:4131–4140
Pullipparacharuvil S, Renthal W, Hale CF, Taniguchi M, Xiao G, Kumar A, Russo SJ, Sikder D, Dewey CM, Davis MM, Greengard P, Naim AC, Nestler EJ, Cowan CW (2008) Cocaine regulates MEF2 to control synaptic and behavioural plasticity. Neuron 59:621–633
Ramachandran B, Yu G, Li S, Zhu B, Gullick T (2008) Myocyte enhancer factor 2A is transcriptionally autoregulated. J Biol Chem 283:10318–10329
Robison AJ, Nestler EJ (2011) Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci 12:623–637
Salma J, McDermott JC (2012) Suppression of a MEF2-KLF6 survival pathway by PKA signalling promotes apoptosis in embryonic hippocampal neurons. J Neurosci 22:2790–2803
Sartorelli V, Huang J, Hamamori Y, Kedes L (1997) Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C. Mol Cell Biol 17:1010–1026
Szczepanek K, Lesnefsky EJ, Larner A (2012) Multi-tasking: nuclear transcription factors with novel roles in the mitochondria. Trends Cell Biol 22:429–437
Sekiyama Y, Suzuki H, Tsukuhara T (2012) Functional gene expression analysis of tissue-specific isoforms of Mef2c. Cell Mol Neurobiol 32:129–139
Shalizi A, Bonni A (2005) Brawn for brains: the role of MEF2 proteins in the developing nervous system. Curr Top Dev Biol 69:239–266
Shalizi A, Gaudillière B, Yuan Z, Stegmuller J, Shirogane T, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A (2006) A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311:1012–1017
She H, Yang Q, Shepherd K, Smith Y, Miller G, Testa C, Mao Z (2011) Direct regulation of complex I by mitochondrial MEF2D is disrupted in a mouse model of Parkinson disease and in human patients. J Clin Invest 121:930–940
She H, Yang Q, Mao Z (2012) Neurotoxin-induced selective ubiquitination and regulation of MEF2A isoform in neuronal stress response. J Neurochem 122:1203–1210
Sheperd JD, Bear MF (2011) New views of Arc, a master regulator of synaptic plasticity. Nature Neurosci 14:279–284
Smith DS, Greer PL, Tsai LH (2001) Cdk5 on the brain. Cell Growth Differ 12:277–283
Smith PD, Mount MP, Shree R, Callaghan S, Slack RS, Anisman H, Vincent I, Wang X, Mao Z, Park DS (2006) Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J Neurosci 26:440–447
Suzaki Y, Yoshizumi M, Kagami S, Koyama AH, Taketani Y, Houchi H, Tsuchiya K, Tamaki T (2002) Hydrogen peroxide stimulates c-src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signalling pathway in PC12 cells. J Biol Chem 277:9614–9621
Takatalo MS, Kouvonen P, Corthals G, Nyman TA, Ronnholm RH (2006) Identification of new Golgi complex specific proteins by direct organelle proteomic analysis. Proteomics 6:3502–3508
Tang X, Wang X, Gong X, Tong M, Park D, Xia Z, Mao Z (2005) Cyclin-dependent kinase 5 mediates neurotoxin-induced degradation of the transcription factor myocyte enhancer factor 2. J Neurosci 25:4823–4834
Taniguchi M, Carreira MB, Smith LN, Zirlin BC, Neve RL, Cowan CW (2012) Histone deacetylase 5 limits cocaine reward through cAMP-induced nuclear import. Neuron 73:108–120
Tian X, Kai L, Hockberger PE, Wokosin DL, Surmeier DJ (2010) MEF-2 regulates activity-dependent spine loss in striatopallidal medium spiny neurons. Mol Cell Neurosci 44:94–108
Vetere G, Restivo L, Cole CJ, Ross PJ, Ammassari-Teule M, Josselyn SA, Frankland PW (2011) Spine growth in the anterior cingulated cortex is necessary for the consolidation of contextual fear memory. Proc Natl Acad Sci USA 108:8456–8460
Wang H, Pineda VV, Chan GC, Wong ST, Muglia LJ, Storm DR (2003) Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. J Neurosci 23:9710–9718
Wang X, Tang X, Li M, Marshall J, Mao Z (2005) Regulation of neuroprotective activity of myocyte-enhancer factor 2 by cAMP-protein kinase A signaling pathway in neuronal survival. J Biol Chem 280:16705–16713
Wang X, She H, Mao Z (2009) Phosphorylation of neuronal survival factor MEF2D by glycogen synthase kinase 3beta in neuronal apoptosis.J Biol Chem 284:32619-32626
West AE, Griffith EC, Greenberg ME (2002) Regulation of transcription factors by neuronal activity. Nat Rev Neurosci 3:921–931
Yang Q, She H, Gearing M, Colla E, Lee M, Shacka JJ, Mao Z (2009) Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323:124–127
Yao L, Li W, She H, Dou J, Jia L, He Y, Yang Q, Capiro NL, Walker D, Pennell KD, Pang Y, Liu Y, Han Y, Mao Z (2012) Activation of transcription factor MEF2D by bis(3)-cognitin protects dopaminergic neurons and ameliorates Parkinsonian motor effects. J Biol Chem 287:34246–34255
Yin Y, She H, Li W, Yang Q, Guo S, Mao Z (2012) Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease. Front Physiol 3:171
Yu T, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B (1992) Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev 6:1783–1798
Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, Olson EN, Ulevitch RJ, Han J (1999) Regulation of the MEF2 family of transcription factors by p38. Mol Cell Biol 19:21–30
Zhong Y, Takemoto M, Fukuda T, Hattori Y, Murakami F, Nakajima D, Nakayama M, Yamamoto N (2004) Identification of the genes that are expressed in the upper layers of the neocortex. Cereb Cortex 14:1144–1152
Zhu B, Gulick T (2004) Phosphorylation and alternative pre-mRNA splicing converge to regulate myocyte enhancer factor 2C activity. Mol Cell Biol 24:8264–8275
Zhu B, Ramachandran B, Gulick T (2005) Alternative pre-mRNA splicing governs expression of a conserved acidic transactivation domain in myocyte enhancer factor 2 factors of striated muscle and brain. J Biol Chem 280:28749–28760
Zweier M, Gregor A, Zweier C, Engels H, Sticht H, Wohlleber E, Bijlsma EK, Holder SE, Zenker M, Rossier E, Grasshoff U, Johnson DS, Robertson L, Firth HV, Kraus C, Ekici AB, Reis A, Rauch A (2010) Mutations in MEF2C from the 5q14.3q15 microdeletion region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. Hum Mutat 31:722–733
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Thanks are due to Anne-Claire Dietrich for the figure.
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Dietrich, JB. The MEF2 family and the brain: from molecules to memory. Cell Tissue Res 352, 179–190 (2013). https://doi.org/10.1007/s00441-013-1565-2
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DOI: https://doi.org/10.1007/s00441-013-1565-2