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MEF2C
Identifiers
Aliases	MEF2C, C5DELq14.3, DEL5q14.3, myocyte enhancer factor 2C
External IDs	OMIM: 600662; MGI: 99458; HomoloGene: 31087; GeneCards: MEF2C; OMA:MEF2C - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q14.3 Start 88,717,117 bp End 88,904,257 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus glutes biceps brachii Skeletal muscle tissue of biceps brachii Brodmann area 23 Skeletal muscle tissue of rectus abdominis vastus lateralis muscle triceps brachii muscle orbitofrontal cortex frontal pole n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein dimerization activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific histone deacetylase binding RNA polymerase II general transcription initiation factor activity core promoter sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding HMG box domain binding RNA polymerase II cis-regulatory region sequence-specific DNA binding minor groove of adenine-thymine-rich DNA binding chromatin binding cis-regulatory region sequence-specific DNA binding protein binding DNA binding sequence-specific DNA binding protein heterodimerization activity transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nuclear speck intracellular membrane-bounded organelle nucleoplasm cytoplasm postsynapse sarcoplasm protein-containing complex Biological process negative regulation of neuron apoptotic process embryonic skeletal system morphogenesis myotube differentiation positive regulation of skeletal muscle tissue development cell morphogenesis involved in neuron differentiation positive regulation of muscle cell differentiation regulation of synapse assembly muscle organ development outflow tract morphogenesis monocyte differentiation sinoatrial valve morphogenesis negative regulation of ossification heart looping positive regulation of skeletal muscle cell differentiation blood vessel remodeling blood vessel development positive regulation of cardiac muscle cell proliferation humoral immune response positive regulation of alkaline phosphatase activity negative regulation of epithelial cell proliferation regulation of synaptic transmission, glutamatergic melanocyte differentiation apoptotic process B cell receptor signaling pathway cellular response to calcium ion cellular response to transforming growth factor beta stimulus renal tubule morphogenesis nephron tubule epithelial cell differentiation cell fate commitment cardiac ventricle formation regulation of transcription, DNA-templated cardiac muscle cell differentiation regulation of neuron apoptotic process platelet formation neuron development smooth muscle cell differentiation positive regulation of protein homodimerization activity negative regulation of gene expression transcription, DNA-templated cellular response to trichostatin A positive regulation of transcription, DNA-templated heart development epithelial cell proliferation involved in renal tubule morphogenesis cardiac muscle hypertrophy in response to stress positive regulation of B cell proliferation positive regulation of neuron differentiation excitatory postsynaptic potential learning or memory positive regulation of macrophage apoptotic process positive regulation of cardiac muscle cell differentiation cellular response to parathyroid hormone stimulus primary heart field specification secondary heart field specification regulation of dendritic spine development regulation of germinal center formation roof of mouth development cell differentiation chondrocyte differentiation positive regulation of bone mineralization neural crest cell differentiation neuron migration B cell homeostasis negative regulation of transcription by RNA polymerase II endochondral ossification regulation of neurotransmitter secretion cellular response to fluid shear stress nervous system development regulation of synaptic plasticity regulation of NMDA receptor activity muscle cell fate determination positive regulation of osteoblast differentiation regulation of synaptic activity osteoblast differentiation neuron differentiation regulation of sarcomere organization skeletal muscle cell differentiation positive regulation of behavioral fear response glomerulus morphogenesis germinal center formation positive regulation of cell proliferation in bone marrow MAPK cascade regulation of AMPA receptor activity multicellular organism development B cell proliferation positive regulation of gene expression positive regulation of myoblast differentiation cartilage morphogenesis embryonic viscerocranium morphogenesis ventricular cardiac muscle cell differentiation cellular response to lipopolysaccharide skeletal muscle tissue development regulation of megakaryocyte differentiation positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II negative regulation of blood vessel endothelial cell migration negative regulation of vascular associated smooth muscle cell proliferation negative regulation of vascular associated smooth muscle cell migration negative regulation of vascular endothelial cell proliferation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4208 17260 Ensembl ENSG00000081189 ENSMUSG00000005583 UniProt Q06413 Q8CFN5 RefSeq (mRNA) NM_001131005 NM_001193347 NM_001193348 NM_001193349 NM_001193350 NM_001308002 NM_002397 NM_001363581 NM_001170537 NM_025282 RefSeq (protein) NP_001124477 NP_001180276 NP_001180277 NP_001180278 NP_001180279 NP_001294931 NP_002388 NP_001350510 NP_001351258 NP_001351259 NP_001351260 NP_001351261 NP_001351262 NP_001351263 NP_001351264 NP_001351265 NP_001351266 NP_001351267 NP_001351268 NP_001351269 NP_001351270 NP_001351271 NP_001351272 NP_001351273 NP_001351274 NP_001351275 NP_001351276 NP_001351277 NP_001351278 NP_001351279 NP_001351281 NP_001351282 NP_001351283 NP_001351284 NP_001351285 NP_001351286 NP_001294931.1 NP_001164008 NP_001334493 NP_001334495 NP_001334496 NP_001334497 NP_001334498 NP_001334500 NP_001334501 NP_001334502 NP_001334503 NP_001334504 NP_001334505 NP_001334506 NP_001334507 NP_001334508 NP_001334509 NP_001334510 NP_079558 Location (UCSC) Chr 5: 88.72 – 88.9 Mb n/a PubMed search
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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. MEF2C is a transcription factor in the Mef2 family.

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,
• HDAC4, HDAC7, HDAC9,
• MAPK7,
• SOX18
• SP1, and
• TEAD1.

• SETD1A

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. It is one of the targets of an oncomiR, MIRN21.

In humans mutations of this gene result in autosomal dominant mental retardation 20 (MRD20), 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

MEF2C-binding site is associated with minor allele of SNP rs630923, associated with the risk of multiple sclerosis, and responsible for reduced CXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response

See also

• Mef2

References

1. ^ GRCh38: Ensembl release 89: ENSG00000081189 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. 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. Bibcode:1993PNAS...90.1546L. doi:10.1073/pnas.90.4.1546. PMC 45911. PMID 7679508.
5. 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.
6. 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.
7. "Entrez Gene: MEF2C myocyte enhancer factor 2C".
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. Online Mendelian Inheritance in Man (OMIM): 613443
17. 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. 153B (5): 1042–51. doi:10.1002/ajmg.b.31071. PMID 20333642. S2CID 3895117.
18. Mitkin NA, Muratova AM, Schwartz AM, Kuprash DV (Nov 2016). "The A Allele of the Single-Nucleotide Polymorphism rs630923 Creates a Binding Site for MEF2C Resulting in Reduced CXCR5 Promoter Activity in B-Cell Lymphoblastic Cell Lines". Front. Immunol. 7 (515): 515. doi:10.3389/fimmu.2016.00515. PMC 5112242. PMID 27909439.

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. Bibcode:1993PNAS...90.1546L. 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. Bibcode:1997Natur.386..296H. doi:10.1038/386296a0. PMID 9069290. S2CID 4234197.
• 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. Bibcode:2000PNAS...97.4070L. 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook MEF2C

• Genes on human chromosome 5
• Transcription factors