This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakatsuji, Y Articles by Sakoda, S Search for Related Content PubMed PubMed Citation Articles by Nakatsuji, Y Articles by Sakoda, S

 Previous Article  |  Next Article 

Mol Cell Biol. 1992 October; 12(10): 4384-4390

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.

Y Nakatsuji, K Hidaka, S Tsujino, Y Yamamoto, T Mukai, T Yanagihara, T Kishimoto and S Sakoda

Department of Medicine III, Osaka University Hospital, Japan.

ABSTRACT

In order to analyze the transcriptional regulation of the muscle-specific subunit of the human phosphoglycerate mutase (PGAM-M) gene, chimeric genes composed of the upstream region of the PGAM-M gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were constructed and transfected into C2C12 skeletal myocytes, primary cultured cardiac muscle cells, and C3H10T1/2 fibroblasts. The expression of chimeric reporter genes was restricted in skeletal and cardiac muscle cells. In C2C12 myotubes and primary cultured cardiac muscle cells, the segment between nucleotides -165 and +41 relative to the transcription initiation site was sufficient to confer maximal CAT activity. This region contains two E boxes and one MEF-2 motif. Deletion and substitution mutation analysis showed that a single MEF-2 motif but not the E boxes had a substantial effect on skeletal and cardiac muscle-specific enhancer activity and that the cardiac muscle-specific negative regulatory region was located between nucleotides -505 and -165. When the PGAM-M gene constructs were cotransfected with MyoD into C3H10T1/2, the profile of CAT activity was similar to that observed in C2C12 myotubes. Gel mobility shift analysis revealed that when the nuclear extracts from skeletal and cardiac muscle cells were used, the PGAM-M MEF-2 site generated the specific band that was inhibited by unlabeled PGAM-M MEF-2 and muscle creatine kinase MEF-2 oligomers but not by a mutant PGAM-M MEF-2 oligomer. These observations define the PGAM-M enhancer as the only cardiac- and skeletal-muscle-specific enhancer characterized thus far that is mainly activated through MEF-2.

---

Mol Cell Biol. 1992 October; 12(10): 4384-4390

This article has been cited by other articles:

• Moyes, C. D., LeMoine, C. M. R. (2005). Control of muscle bioenergetic gene expression: implications for allometric scaling relationships of glycolytic and oxidative enzymes. J. Exp. Biol. 208: 1601-1610 [Abstract] [Full Text]  
• Hughes, S. M., Chi, M. M.-Y., Lowry, O. H., Gundersen, K. (1999). Myogenin Induces a Shift of Enzyme Activity from Glycolytic to Oxidative Metabolism in Muscles of Transgenic Mice. JCB 145: 633-642 [Abstract] [Full Text]  
• Ruiz-Lozano, P., Hixon, M. L., Wagner, M. W., Flores, A. I., Ikawa, S., Baldwin, A. S. Jr., Chien, K. R., Gualberto, A. (1999). p53 Is a Transcriptional Activator of the Muscle-specific Phosphoglycerate Mutase Gene and Contributesin Vivo to the Control of Its Cardiac Expression. Cell Growth Differ. 10: 295-306 [Abstract] [Full Text]  
• Kell, R., Pierce, H., Swoap, S. J. (1999). PGAM-M expression is regulated pretranslationally in hindlimb muscles and under altered loading conditions. J. Appl. Physiol. 86: 236-242 [Abstract] [Full Text]  
• Kimura, S., Fujishita, S., Ikezawa, M., Ogawa, M., Abe, K., Miike, T. (1998). Muscle Type Promoter and Its First Intron Abnormalities in Dystrophin Gene in Patients With Duchenne Muscular Dystrophy. J Child Neurol 13: 290-292  
• Ornatsky, O. I., McDermott, J. C. (1996). MEF2 Protein Expression, DNA Binding Specificity and Complex Composition, and Transcriptional Activity in Muscle and Non-muscle Cells. J. Biol. Chem. 271: 24927-24933 [Abstract] [Full Text]  
• Mably, J. D., Liew, C.-C. (1996). Factors Involved in Cardiogenesis and the Regulation of Cardiac-Specific Gene Expression. Circ. Res. 79: 4-13 [Abstract] [Full Text]  
• Schmoelzl, S., Leeb, T., Brinkmeier, H., Brem, G., Brenig, B. (1996). Regulation of Tissue-specific Expression of the Skeletal Muscle Ryanodine Receptor Gene. J. Biol. Chem. 271: 4763-4769 [Abstract] [Full Text]  
• Bour, B A, O'Brien, M A, Lockwood, W L, Goldstein, E S, Bodmer, R, Taghert, P H, Abmayr, S M, Nguyen, H T (1995). Drosophila MEF2, a transcription factor that is essential for myogenesis.. Genes Dev. 9: 730-741 [Abstract]  
• Kaushal, S, Schneider, J., Nadal-Ginard, B, Mahdavi, V (1994). Activation of the myogenic lineage by MEF2A, a factor that induces and cooperates with MyoD. Science 266: 1236-1240 [Abstract]  
• Chambers, A E, Logan, M, Kotecha, S, Towers, N, Sparrow, D, Mohun, T J (1994). The RSRF/MEF2 protein SL1 regulates cardiac muscle-specific transcription of a myosin light-chain gene in Xenopus embryos.. Genes Dev. 8: 1324-1334 [Abstract]  
• Edmondson, D., Lyons, G., Martin, J., Olson, E. (1994). Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis. Development 120: 1251-1263 [Abstract]  
• Breitbart, R., Liang, C., Smoot, L., Laheru, D., Mahdavi, V, Nadal-Ginard, B (1993). A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development 118: 1095-1106 [Abstract]