From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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 .
[4]
[5] MEF2C is a
transcription factor in the
Mef2 family.
[6]
[7]
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 kilo
daltons . 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:
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 .
[15] It is one of the targets of an oncomiR,
MIRN21 .
In humans mutations of this gene result in
autosomal dominant mental retardation 20 (MRD20),
[16] 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
[17]
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
[18]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000081189 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ 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 .
^ 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 .
^ 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 .
^
"Entrez Gene: MEF2C myocyte enhancer factor 2C" .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^
Online Mendelian Inheritance in Man (OMIM):
613443
^ 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 .
^ 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
(1) Basic domains
(1.1) Basic
leucine zipper (
bZIP )(1.2) Basic helix-loop-helix (
bHLH )
Group A Group B Group C bHLH-
PAS Group D Group E Group F bHLH-COE
(1.3)
bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2)
Zinc finger DNA-binding domains
(2.1)
Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors