Myocyte Enhancer Factor (MEF) 2C: a Tissue-restricted Member of the MEF-2 Family of Transcription Factors

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Jun 1

PMID 8506376

Citations 88

Authors

J F Martin

J J Schwarz

E N Olson

Affiliations

Soon will be listed here.

Abstract

MEF-2 is a muscle-specific DNA binding activity that recognizes an A+T-rich sequence found in the control regions of numerous muscle-specific genes. The recent cloning of MEF-2 showed that it belongs to the MADS (MCM1, Agamous, Deficiens, and serum-response factor) box family of transcription factors and that MEF-2 mRNA is expressed ubiquitously. Here we describe the cloning of a member of the MEF-2 gene family, referred to as MEF-2C, that is nearly identical to other MEF-2 gene products in the MADS box but diverges from other members of the family outside of this domain. MEF-2C binds the MEF-2 site with high affinity and can activate transcription of a reporter gene linked to tandem copies of that site. In contrast to previously described members of the MEF-2 family, MEF-2C transcripts are highly enriched in skeletal muscle, spleen, and brain of adult mice and are upregulated during myoblast differentiation. These results suggest that the MEF-2 site is a target for a diverse family of proteins that regulates transcription in a variety of cell types.

Citing Articles

Mef2c Controls Postnatal Callosal Axon Targeting by Regulating Sensitivity to Ephrin Repulsion.

Sudarsanam S, Guzman-Clavel L, Dar N, Ziak J, Shahid N, Jin X bioRxiv. 2025; .

PMID: 39896513 PMC: 11785193. DOI: 10.1101/2025.01.22.634300.

Mef2c- and Nkx2-5-Divergent Transcriptional Regulation of Chick WT1_76127 and Mouse Gm14014 lncRNAs and Their Implication in Epicardial Cell Migration.

Cano-Carrillo S, Garcia-Padilla C, Aranega A, Lozano-Velasco E, Franco D Int J Mol Sci. 2024; 25(23).

PMID: 39684625 PMC: 11640978. DOI: 10.3390/ijms252312904.

Dysregulation of miRNA expression and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids.

Trudler D, Ghatak S, Bula M, Parker J, Talantova M, Luevanos M Mol Psychiatry. 2024; .

PMID: 39349966 DOI: 10.1038/s41380-024-02761-9.

Myotube Guidance: Shaping up the Musculoskeletal System.

Johnson A J Dev Biol. 2024; 12(3).

PMID: 39311120 PMC: 11417883. DOI: 10.3390/jdb12030025.

MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-Transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Member Expression.

Lozano-Velasco E, Garcia-Padilla C, Carmona-Garcia M, Gonzalez-Diaz A, Arequipa-Rendon A, Aranega A Noncoding RNA. 2024; 10(3).

PMID: 38804364 PMC: 11130849. DOI: 10.3390/ncrna10030032.

References

Schwarz-Sommer Z, Huijser P, Nacken W, Saedler H, Sommer H . Genetic Control of Flower Development by Homeotic Genes in Antirrhinum majus. Science. 1990; 250(4983):931-6. DOI: 10.1126/science.250.4983.931. View

Nakatsuji Y, Hidaka K, Tsujino S, Yamamoto Y, Mukai T, Yanagihara T . A single MEF-2 site is a major positive regulatory element required for transcription of the muscle-specific subunit of the human phosphoglycerate mutase gene in skeletal and cardiac muscle cells. Mol Cell Biol. 1992; 12(10):4384-90. PMC: 360362. DOI: 10.1128/mcb.12.10.4384-4390.1992. View

Muscat G, Perry S, Prentice H, Kedes L . The human skeletal alpha-actin gene is regulated by a muscle-specific enhancer that binds three nuclear factors. Gene Expr. 1992; 2(2):111-26. PMC: 6057388. View

Grueneberg D, Natesan S, Alexandre C, Gilman M . Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. Science. 1992; 257(5073):1089-95. DOI: 10.1126/science.257.5073.1089. View

Yanofsky M, Ma H, Bowman J, Drews G, Feldmann K, Meyerowitz E . The protein encoded by the Arabidopsis homeotic gene agamous resembles transcription factors. Nature. 1990; 346(6279):35-9. DOI: 10.1038/346035a0. View

Buskin J, Hauschka S . Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Mol Cell Biol. 1989; 9(6):2627-40. PMC: 362335. DOI: 10.1128/mcb.9.6.2627-2640.1989. View

Edmondson D, Cheng T, Cserjesi P, Chakraborty T, Olson E . Analysis of the myogenin promoter reveals an indirect pathway for positive autoregulation mediated by the muscle-specific enhancer factor MEF-2. Mol Cell Biol. 1992; 12(9):3665-77. PMC: 360220. DOI: 10.1128/mcb.12.9.3665-3677.1992. View

Dalton S, Treisman R . Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992; 68(3):597-612. DOI: 10.1016/0092-8674(92)90194-h. View

Edmondson D, Olson E . A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989; 3(5):628-40. DOI: 10.1101/gad.3.5.628. View

10.

Lassar A, Davis R, Wright W, Kadesch T, Murre C, Voronova A . Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991; 66(2):305-15. DOI: 10.1016/0092-8674(91)90620-e. View

11.

Norman C, Runswick M, Pollock R, Treisman R . Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988; 55(6):989-1003. DOI: 10.1016/0092-8674(88)90244-9. View

12.

Horlick R, Hobson G, Patterson J, MITCHELL M, Benfield P . Brain and muscle creatine kinase genes contain common TA-rich recognition protein-binding regulatory elements. Mol Cell Biol. 1990; 10(9):4826-36. PMC: 361091. DOI: 10.1128/mcb.10.9.4826-4836.1990. View

13.

Edmondson D, Olson E . Helix-loop-helix proteins as regulators of muscle-specific transcription. J Biol Chem. 1993; 268(2):755-8. View

14.

Passmore S, Maine G, Elble R, Christ C, Tye B . Saccharomyces cerevisiae protein involved in plasmid maintenance is necessary for mating of MAT alpha cells. J Mol Biol. 1988; 204(3):593-606. DOI: 10.1016/0022-2836(88)90358-0. View

15.

Iannello R, Mar J, Ordahl C . Characterization of a promoter element required for transcription in myocardial cells. J Biol Chem. 1991; 266(5):3309-16. View

16.

Braun T, Tannich E, Arnold H . Promoter upstream elements of the chicken cardiac myosin light-chain 2-A gene interact with trans-acting regulatory factors for muscle-specific transcription. Mol Cell Biol. 1989; 9(6):2513-25. PMC: 362324. DOI: 10.1128/mcb.9.6.2513-2525.1989. View

17.

Cserjesi P, Olson E . Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products. Mol Cell Biol. 1991; 11(10):4854-62. PMC: 361454. DOI: 10.1128/mcb.11.10.4854-4862.1991. View

18.

Mueller C, Nordheim A . A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation. EMBO J. 1991; 10(13):4219-29. PMC: 453174. DOI: 10.1002/j.1460-2075.1991.tb05000.x. View

19.

Yu Y, Breitbart R, Smoot L, Lee Y, Mahdavi V, Nadal-Ginard B . Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 1992; 6(9):1783-98. DOI: 10.1101/gad.6.9.1783. View

20.

Hipskind R, Rao V, Mueller C, Reddy E, Nordheim A . Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature. 1991; 354(6354):531-4. DOI: 10.1038/354531a0. View