MEF2C

Myocyte enhancer factor 2C
PDB rendering based on 1c7u.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1c7u​, 1egw​
Identifiers
Symbols	MEF2C ; C5DELq14.3; DEL5q14.3
External IDs	OMIM: 600662 MGI: 99458 HomoloGene: 31087 GeneCards: MEF2C Gene
Gene ontology Molecular function • RNA polymerase II regulatory region sequence-specific DNA binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcription factor activity, RNA polymerase II core promoter sequence-specific • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • AT DNA binding • transcription factor activity, sequence-specific DNA binding • protein binding • activating transcription factor binding • miRNA binding • transcription regulatory region DNA binding • protein heterodimerization activity Cellular component • nucleus • nucleoplasm • cytoplasm • cytosol • nuclear speck • intracellular membrane-bounded organelle • protein complex Biological process • negative regulation of transcription from RNA polymerase II promoter • MAPK cascade • blood vessel development • osteoblast differentiation • neuron migration • B cell homeostasis • heart looping • endochondral ossification • blood vessel remodeling • chondrocyte differentiation • toll-like receptor signaling pathway • germinal center formation • regulation of germinal center formation • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • response to ischemia • primary heart field specification • secondary heart field specification • outflow tract morphogenesis • sinoatrial valve morphogenesis • cardiac ventricle formation • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • apoptotic process • humoral immune response • nervous system development • heart development • muscle organ development • skeletal muscle tissue development • muscle cell fate determination • learning or memory • response to virus • positive regulation of gene expression • negative regulation of gene expression • positive regulation of alkaline phosphatase activity • neural crest cell differentiation • myotube differentiation • neuron differentiation • platelet formation • negative regulation of ossification • melanocyte differentiation • positive regulation of bone mineralization • positive regulation of B cell proliferation • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • TRIF-dependent toll-like receptor signaling pathway • cellular response to drug • cellular response to trichostatin A • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • B cell proliferation • muscle cell differentiation • positive regulation of MAP kinase activity • regulation of neuron apoptotic process • negative regulation of neuron apoptotic process • innate immune response • regulation of megakaryocyte differentiation • positive regulation of myoblast differentiation • positive regulation of neuron differentiation • positive regulation of osteoblast differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • regulation of neurotransmitter secretion • neurotrophin TRK receptor signaling pathway • regulation of synaptic plasticity • positive regulation of skeletal muscle tissue development • neuron development • cell morphogenesis involved in neuron differentiation • B cell receptor signaling pathway • smooth muscle cell differentiation • positive regulation of muscle cell differentiation • stress-activated MAPK cascade • regulation of synapse assembly • regulation of synaptic transmission, glutamatergic • ventricular cardiac muscle cell differentiation • regulation of synaptic activity • positive regulation of cardiac muscle cell proliferation • excitatory postsynaptic potential • regulation of dendritic spine development • renal tubule morphogenesis • cellular response to lipopolysaccharide • cellular response to calcium ion • cellular response to parathyroid hormone stimulus • cellular response to fluid shear stress • cellular response to transforming growth factor beta stimulus • glomerulus morphogenesis • nephron tubule epithelial cell differentiation • positive regulation of protein homodimerization activity • positive regulation of macrophage apoptotic process • regulation of N-methyl-D-aspartate selective glutamate receptor activity • regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity • positive regulation of cardiac muscle cell differentiation • positive regulation of behavioral fear response • epithelial cell proliferation involved in renal tubule morphogenesis • positive regulation of skeletal muscle cell differentiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4208	17260
Ensembl	ENSG00000081189	ENSMUSG00000005583
UniProt	Q06413	Q8CFN5
RefSeq (mRNA)	NM_001131005	NM_001170537
RefSeq (protein)	NP_001124477	NP_001164008
Location (UCSC)	Chr 5: 88.72 – 88.9 Mb	Chr 13: 83.5 – 83.67 Mb
PubMed search

Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene.^[1][2] MEF2C is a transcription factor in the Mef2 family.^[3][4]

Genomics

The gene is located at 5q14.3 on the minus (Crick) strand and is 200,723 bases in length. The encoded protein has 473 amino acids with a predicted molecular weight of 51.221 kiloDaltons. Three isoforms have been identified. Several post translational modifications have been identified including phosphorylation on serine-59 and serine-396, sumoylation on lysine-391, acetylation on lysine-4 and proteolytic cleavage.

Interactions

MEF2C has been shown to interact with:

• EP300,^[5]
• HDAC4, HDAC7, HDAC9,^[6][7]
• MAPK7,^[8]
• SOX18^[9]
• SP1,^[10] and
• TEAD1.^[11]

Biological significance

This gene is involved in cardiac morphogenesis and myogenesis and vascular development. It may also be involved in neurogenesis and in the development of cortical architecture. Mice without a functional copy of the Mef2c gene die before birth and have abnormalities in the heart and vascular system.^[12] It is one of the targets of an oncomiR, MIRN21.

In humans mutations of this gene result in autosomal dominant mental retardation 20 (MRD20),^[13] characterised by severe psychomotor impairment, periodic tremor and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features, mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes^[14]

See also

• Mef2

References

1. Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA (Feb 1993). "MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex". Proceedings of the National Academy of Sciences of the United States of America 90 (4): 1546–50. doi:10.1073/pnas.90.4.1546. PMC 45911. PMID 7679508.
2. McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B (Apr 1993). "hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors". Molecular and Cellular Biology 13 (4): 2564–77. doi:10.1128/mcb.13.4.2564. PMC 359588. PMID 8455629.
3. Molkentin JD, Black BL, Martin JF, Olson EN (Jun 1996). "Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C". Molecular and Cellular Biology 16 (6): 2627–36. doi:10.1128/mcb.16.6.2627. PMC 231253. PMID 8649370.
4. "Entrez Gene: MEF2C myocyte enhancer factor 2C".
5. Sartorelli V, Huang J, Hamamori Y, Kedes L (Feb 1997). "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Molecular and Cellular Biology 17 (2): 1010–26. doi:10.1128/mcb.17.2.1010. PMC 231826. PMID 9001254.
6. Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (Nov 1999). "HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor". Molecular and Cellular Biology 19 (11): 7816–27. doi:10.1128/mcb.19.11.7816. PMC 84849. PMID 10523670.
7. Wang AH, Yang XJ (Sep 2001). "Histone deacetylase 4 possesses intrinsic nuclear import and export signals". Molecular and Cellular Biology 21 (17): 5992–6005. doi:10.1128/MCB.21.17.5992-6005.2001. PMC 87317. PMID 11486037.
8. Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (Oct 1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research 26 (20): 4771–7. doi:10.1093/nar/26.20.4771. PMC 147902. PMID 9753748.
9. Hosking BM, Wang SC, Chen SL, Penning S, Koopman P, Muscat GE (Sep 2001). "SOX18 directly interacts with MEF2C in endothelial cells". Biochemical and Biophysical Research Communications 287 (2): 493–500. doi:10.1006/bbrc.2001.5589. PMID 11554755.
10. Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, Lipton SA (Oct 1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". The Journal of Biological Chemistry 273 (40): 26218–24. doi:10.1074/jbc.273.40.26218. PMID 9748305.
11. Maeda T, Gupta MP, Stewart AF (Jun 2002). "TEF-1 and MEF2 transcription factors interact to regulate muscle-specific promoters". Biochemical and Biophysical Research Communications 294 (4): 791–7. doi:10.1016/S0006-291X(02)00556-9. PMID 12061776.
12. Bi W, Drake CJ, Schwarz JJ (Jul 1999). "The transcription factor MEF2C-null mouse exhibits complex vascular malformations and reduced cardiac expression of angiopoietin 1 and VEGF". Developmental Biology 211 (2): 255–67. doi:10.1006/dbio.1999.9307. PMID 10395786.
13. Online 'Mendelian Inheritance in Man' (OMIM) 613443
14. Nowakowska BA, Obersztyn E, Szymańska K, Bekiesińska-Figatowska M, Xia Z, Ricks CB, Bocian E, Stockton DW, Szczałuba K, Nawara M, Patel A, Scott DA, Cheung SW, Bohan TP, Stankiewicz P (Jul 2010). "Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 153B (5): 1042–51. doi:10.1002/ajmg.b.31071. PMID 20333642.

Further reading

• Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA (Feb 1993). "MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex". Proceedings of the National Academy of Sciences of the United States of America 90 (4): 1546–50. doi:10.1073/pnas.90.4.1546. PMC 45911. PMID 7679508.
• Hobson GM, Krahe R, Garcia E, Siciliano MJ, Funanage VL (Oct 1995). "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". Genomics 29 (3): 704–11. doi:10.1006/geno.1995.9007. PMID 8575763.
• Krainc D, Haas M, Ward DC, Lipton SA, Bruns G, Leifer D (Oct 1995). "Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved". Genomics 29 (3): 809–11. doi:10.1006/geno.1995.9927. PMID 8575784.
• Molkentin JD, Li L, Olson EN (Jul 1996). "Phosphorylation of the MADS-Box transcription factor MEF2C enhances its DNA binding activity". The Journal of Biological Chemistry 271 (29): 17199–204. doi:10.1074/jbc.271.29.17199. PMID 8663403.
• Black BL, Ligon KL, Zhang Y, Olson EN (Oct 1996). "Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family". The Journal of Biological Chemistry 271 (43): 26659–63. doi:10.1074/jbc.271.43.26659. PMID 8900141.
• Gradwohl G, Fode C, Guillemot F (Nov 1996). "Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors". Developmental Biology 180 (1): 227–41. doi:10.1006/dbio.1996.0297. PMID 8948587.
• Sartorelli V, Huang J, Hamamori Y, Kedes L (Feb 1997). "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Molecular and Cellular Biology 17 (2): 1010–26. doi:10.1128/mcb.17.2.1010. PMC 231826. PMID 9001254.
• Han J, Jiang Y, Li Z, Kravchenko VV, Ulevitch RJ (Mar 1997). "Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation". Nature 386 (6622): 296–9. doi:10.1038/386296a0. PMID 9069290.
• Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (Dec 1997). "BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C". The EMBO Journal 16 (23): 7054–66. doi:10.1093/emboj/16.23.7054. PMC 1170308. PMID 9384584.
• Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, Lipton SA (Oct 1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". The Journal of Biological Chemistry 273 (40): 26218–24. doi:10.1074/jbc.273.40.26218. PMID 9748305.
• Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (Oct 1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research 26 (20): 4771–7. doi:10.1093/nar/26.20.4771. PMC 147902. PMID 9753748.
• Swanson BJ, Jäck HM, Lyons GE (Jun 1998). "Characterization of myocyte enhancer factor 2 (MEF2) expression in B and T cells: MEF2C is a B cell-restricted transcription factor in lymphocytes". Molecular Immunology 35 (8): 445–58. doi:10.1016/S0161-5890(98)00058-3. PMID 9798649.
• Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, Olson EN, Ulevitch RJ, Han J (Jan 1999). "Regulation of the MEF2 family of transcription factors by p38". Molecular and Cellular Biology 19 (1): 21–30. doi:10.1128/mcb.19.1.21. PMC 83862. PMID 9858528.
• Wilson-Rawls J, Molkentin JD, Black BL, Olson EN (Apr 1999). "Activated notch inhibits myogenic activity of the MADS-Box transcription factor myocyte enhancer factor 2C". Molecular and Cellular Biology 19 (4): 2853–62. doi:10.1128/mcb.19.4.2853. PMC 84078. PMID 10082551.
• Yang SH, Galanis A, Sharrocks AD (Jun 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors". Molecular and Cellular Biology 19 (6): 4028–38. doi:10.1128/mcb.19.6.4028. PMC 104362. PMID 10330143.
• Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (Nov 1999). "HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor". Molecular and Cellular Biology 19 (11): 7816–27. doi:10.1128/mcb.19.11.7816. PMC 84849. PMID 10523670.
• Lu J, McKinsey TA, Nicol RL, Olson EN (Apr 2000). "Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases". Proceedings of the National Academy of Sciences of the United States of America 97 (8): 4070–5. doi:10.1073/pnas.080064097. PMC 18151. PMID 10737771.
• Morin S, Charron F, Robitaille L, Nemer M (May 2000). "GATA-dependent recruitment of MEF2 proteins to target promoters". The EMBO Journal 19 (9): 2046–55. doi:10.1093/emboj/19.9.2046. PMC 305697. PMID 10790371.
• Wu Z, Woodring PJ, Bhakta KS, Tamura K, Wen F, Feramisco JR, Karin M, Wang JY, Puri PL (Jun 2000). "p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple steps". Molecular and Cellular Biology 20 (11): 3951–64. doi:10.1128/MCB.20.11.3951-3964.2000. PMC 85749. PMID 10805738.

External links

• MEF2C protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook MEF2C