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 Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salminen, M Articles by Daegelen, D Search for Related Content PubMed PubMed Citation Articles by Salminen, M Articles by Daegelen, D

Fast-muscle-specific expression of human aldolase A transgenes.

Institut Cochin de Génétique Moléculaire, Université René Descartes, Paris, France.

ABSTRACT

The expression of the human aldolase A gene is controlled by three alternative promoters. In transgenic mice, pN and pH are active in all tissues whereas pM is activated specifically in adult muscles composed mainly of fast, glycolytic fibers. To detect potential regulatory regions involved in the fast-muscle-specific activation of pM, we analyzed DNase I hypersensitivity in a 4.3-kbp fragment from the 5' end of the human aldolase A gene. Five hypersensitive sites were located near the transcription initiation site of each promoter in those transgenic-mouse tissues in which the corresponding promoter was active. Only one muscle-specific hypersensitive site was detected, mapping near pM. To functionally delimit the elements required for muscle-specific activity of pM, we performed a deletion analysis of the aldolase A 5' region in transgenic mice. Our results show that a 280-bp fragment containing 235 bp of pM proximal upstream sequences together with the noncoding M exon is sufficient for tissue-specific expression of pM. When a putative MEF-2-binding site residing in this proximal pM region is mutated, pM is still active and no change in its tissue specificity is detected. Furthermore, we observed a modulation of pM activity by elements lying further upstream and downstream from pM. Interestingly, pM was expressed in a tissue-specific way in all transgenic mice in which the 280-bp region was present (32 lines and six founder animals). This observation led us to suggest that the proximal pM region contains elements that are able to override to some extent the effects of the surrounding chromatin.

This article has been cited by other articles:

• Grifone, R., Laclef, C., Spitz, F., Lopez, S., Demignon, J., Guidotti, J.-E., Kawakami, K., Xu, P.-X., Kelly, R., Petrof, B. J., Daegelen, D., Concordet, J.-P., Maire, P. (2004). Six1 and Eya1 Expression Can Reprogram Adult Muscle from the Slow-Twitch Phenotype into the Fast-Twitch Phenotype. Mol. Cell. Biol. 24: 6253-6267 [Abstract] [Full Text]  
• Bertrand, A., Ngo-Muller, V., Hentzen, D., Concordet, J.-P., Daegelen, D., Tuil, D. (2003). Muscle electrotransfer as a tool for studying muscle fiber-specific and nerve-dependent activity of promoters. Am. J. Physiol. Cell Physiol. 285: C1071-C1081 [Abstract] [Full Text]  
• Vullhorst, D., Buonanno, A. (2003). Characterization of General Transcription Factor 3, a Transcription Factor Involved in Slow Muscle-specific Gene Expression. J. Biol. Chem. 278: 8370-8379 [Abstract] [Full Text]  
• Long, W. P., Chen, X., Perdew, G. H. (1999). Protein Kinase C Modulates Aryl Hydrocarbon Receptor Nuclear Translocator Protein-mediated Transactivation Potential in a Dimer Context. J. Biol. Chem. 274: 12391-12400 [Abstract] [Full Text]  
• Spitz, F., Demignon, J., Porteu, A., Kahn, A., Concordet, J.-P., Daegelen, D., Maire, P. (1998). Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site. Proc. Natl. Acad. Sci. USA 95: 14220-14225 [Abstract] [Full Text]  
• Spitz, F., De Vasconcelos, Z. A., Chatelet, F., Demignon, J., Kahn, A., Mira, J.-C., Maire, P., Daegelen, D. (1998). Proximal Sequences of the Aldolase A Fast Muscle-specific Promoter Direct Nerve- and Activity-dependent Expression in Transgenic Mice. J. Biol. Chem. 273: 14975-14981 [Abstract] [Full Text]  
• Walther, E. U., Dichgans, M., Maricich, S. M., Romito, R. R., Yang, F., Dziennis, S., Zackson, S., Hawkes, R., Herrup, K. (1998). Genomic sequences of aldolase C (Zebrin II) direct lacZ expression exclusively in non-neuronal cells of transgenic mice. Proc. Natl. Acad. Sci. USA 95: 2615-2620 [Abstract] [Full Text]  
• Swoap, S. J. (1998). In vivo analysis of the myosin heavy chain IIB promoter region. Am. J. Physiol. Cell Physiol. 274: C681-C687 [Abstract] [Full Text]  
• Spitz, F., Demignon, J., Demeurie, J., Sabourin, J.-C., Kahn, A., Daegelen, D., Maire, P. (1998). A Binding Site for Nuclear Receptors Is Required for the Differential Expression of the Aldolase A Fast-twitch Muscle Promoter in Body and Head Muscles. J. Biol. Chem. 273: 561-567 [Abstract] [Full Text]  
• Lupo, A., Costanzo, P., Medugno, L., Romeo, I., Salvatore, F., Izzo, P. (1997). Negative Regulation of the Mouse Aldolase A Gene. A CELL CYCLE-DEPENDENT DNA BINDING ACTIVITY FUNCTIONS AS A SILENCER OF GENE TRANSCRIPTION. J. Biol. Chem. 272: 31641-31647 [Abstract] [Full Text]  
• Lewis, A. L., Guicherit, O. M., Datta, S. K., Hanten, G. R., Kellems, R. E. (1996). Structure and Expression of the Murine Muscle Adenylosuccinate Synthetase Gene. J. Biol. Chem. 271: 22647-22656 [Abstract] [Full Text]  
• Hallauer, P. L., Hastings, K. E. M. (2002). Coregulation of fast contractile protein transgene and glycolytic enzyme expression in mouse skeletal muscle. Am. J. Physiol. Cell Physiol. 282: C113-C124 [Abstract] [Full Text]