MEF2B explained

Myocyte enhancer binding factor 2B (MEF2B) is a transcription factor part of the MEF2 gene family including MEF2A, MEF2C, and MEF2D.^{[1] [2]} However, MEF2B is distant from the other three branches of MEF2 genes as it lacks the protein-coding Holliday junction recognition protein C-terminal (HJURP_C) region in vertebrates.^[3]

Functions

The MEF2 gene family is expressed in muscle-specific gene activation and maintenance during development.^[4] MEF2B mRNA is present in skeletal, smooth, brain and heart muscles.^[5] MEF2B is directly involved in smooth muscle myosin heavy chain (SMHC) gene regulation. Overexpression of MEF2B will activate the SMHC promoter in smooth muscle when it is bound to the A/T-rich element of the promoter.

Interactions

MEF2B has been shown to interact with CABIN1.^{[6] [7]}

Clinical relevance

Recurrent mutations in this gene have been associated with cases of diffuse large B-cell lymphoma.^[8] In its mutated form, MEF2B can lead to deregulation of the proto-oncogene BCL6 expression in diffuse large B-cell lymphomas (DLBCL).^[9] Mutations of MEF2B enhance its transcriptional activity due to either a disruption with its corepressor CABIN1 or causing the gene to become insensitive to inhibitory signaling events.

See also

• Mef2

References

Further reading

• Yu YT, Breitbart RE, Smoot LB, Lee Y, Mahdavi V, Nadal-Ginard B . Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors . Genes & Development . 6 . 9 . 1783–1798 . September 1992 . 1516833 . 10.1101/gad.6.9.1783 . free .
• Pollock R, Treisman R . Human SRF-related proteins: DNA-binding properties and potential regulatory targets . Genes & Development . 5 . 12A . 2327–2341 . December 1991 . 1748287 . 10.1101/gad.5.12a.2327 . free .
• Hobson GM, Krahe R, Garcia E, Siciliano MJ, Funanage VL . 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 . 704–711 . October 1995 . 8575763 . 10.1006/geno.1995.9007 .
• Katoh Y, Molkentin JD, Dave V, Olson EN, 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 . The Journal of Biological Chemistry . 273 . 3 . 1511–1518 . January 1998 . 9430690 . 10.1074/jbc.273.3.1511 . free .
• Iida K, Hidaka K, Takeuchi M, Nakayama M, Yutani C, Mukai T, Morisaki T . Expression of MEF2 genes during human cardiac development . The Tohoku Journal of Experimental Medicine . 187 . 1 . 15–23 . January 1999 . 10458488 . 10.1620/tjem.187.15 . free .
• Youn HD, Sun L, Prywes R, Liu JO . Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2 . Science . 286 . 5440 . 790–793 . October 1999 . 10531067 . 10.1126/science.286.5440.790 .
• Li M, Linseman DA, Allen MP, Meintzer MK, Wang X, Laessig T, Wierman ME, Heidenreich KA . Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase-mediated degradation during apoptosis of rat cerebellar granule neurons . The Journal of Neuroscience . 21 . 17 . 6544–6552 . September 2001 . 11517243 . 6763101 . 10.1523/JNEUROSCI.21-17-06544.2001 .
• Han A, Pan F, Stroud JC, Youn HD, Liu JO, Chen L . Sequence-specific recruitment of transcriptional co-repressor Cabin1 by myocyte enhancer factor-2 . Nature . 422 . 6933 . 730–734 . April 2003 . 12700764 . 10.1038/nature01555 . 4430658 . 2003Natur.422..730H .
• Konig S, Hinard V, Arnaudeau S, Holzer N, Potter G, Bader CR, Bernheim L . Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation . The Journal of Biological Chemistry . 279 . 27 . 28187–28196 . July 2004 . 15084602 . 10.1074/jbc.M313932200 . free .
• Han A, He J, Wu Y, Liu JO, Chen L . Mechanism of recruitment of class II histone deacetylases by myocyte enhancer factor-2 . Journal of Molecular Biology . 345 . 1 . 91–102 . January 2005 . 15567413 . 10.1016/j.jmb.2004.10.033 .
• Gong X, Tsai SW, Yan B, Rubin LP . Cooperation between MEF2 and PPARgamma in human intestinal beta,beta-carotene 15,15'-monooxygenase gene expression . BMC Molecular Biology . 7 . 7 . February 2006 . 16504037 . 1526748 . 10.1186/1471-2199-7-7 . free .

Notes and References

1. Krenács D, Borbényi Z, Bedekovics J, Méhes G, Bagdi E, Krenács L . Pattern of MEF2B expression in lymphoid tissues and in malignant lymphomas . Virchows Archiv . 467 . 3 . 345–355 . September 2015 . 26089142 . 10.1007/s00428-015-1796-6 . 25535467 .
2. Rodríguez AI, Csányi G, Ranayhossaini DJ, Feck DM, Blose KJ, Assatourian L, Vorp DA, Pagano PJ . MEF2B-Nox1 signaling is critical for stretch-induced phenotypic modulation of vascular smooth muscle cells . Arteriosclerosis, Thrombosis, and Vascular Biology . 35 . 2 . 430–438 . February 2015 . 25550204 . 4409426 . 10.1161/ATVBAHA.114.304936 .
3. Wu W, de Folter S, Shen X, Zhang W, Tao S . Vertebrate paralogous MEF2 genes: origin, conservation, and evolution . PLOS ONE . 6 . 3 . e17334 . March 2011 . 21394201 . 3048864 . 10.1371/journal.pone.0017334 . free . 2011PLoSO...617334W .
4. Buchberger A, Arnold HH . The MADS domain containing transcription factor cMef2a is expressed in heart and skeletal muscle during embryonic chick development . Development Genes and Evolution . 209 . 6 . 376–381 . June 1999 . 10370120 . 10.1007/s004270050267 . 2819535 .
5. Katoh Y, Molkentin JD, Dave V, Olson EN, 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 . The Journal of Biological Chemistry . 273 . 3 . 1511–1518 . January 1998 . 9430690 . 10.1074/jbc.273.3.1511 . free .
6. Han A, Pan F, Stroud JC, Youn HD, Liu JO, Chen L . Sequence-specific recruitment of transcriptional co-repressor Cabin1 by myocyte enhancer factor-2 . Nature . 422 . 6933 . 730–734 . April 2003 . 12700764 . 10.1038/nature01555 . 4430658 . 2003Natur.422..730H .
7. Youn HD, Sun L, Prywes R, Liu JO . Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2 . Science . 286 . 5440 . 790–793 . October 1999 . 10531067 . 10.1126/science.286.5440.790 .
8. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA . Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma . Nature . 476 . 7360 . 298–303 . July 2011 . 21796119 . 3210554 . 10.1038/nature10351 . 2011Natur.476..298M .
9. Ying CY, Dominguez-Sola D, Fabi M, Lorenz IC, Hussein S, Bansal M, Califano A, Pasqualucci L, Basso K, Dalla-Favera R . MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma . Nature Immunology . 14 . 10 . 1084–1092 . October 2013 . 23974956 . 3954820 . 10.1038/ni.2688 .