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 Concordet, J P Articles by Daegelen, D Search for Related Content PubMed PubMed Citation Articles by Concordet, J P Articles by Daegelen, D

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 January; 13(1): 9-17

An opportunistic promoter sharing regulatory sequences with either a muscle-specific or a ubiquitous promoter in the human aldolase A gene.

Unité de Recherches en Génétique et Pathologie Moléculaires, INSERM U129, ICGM, Paris, France.

ABSTRACT

The human aldolase A gene is transcribed from three different promoters, pN, pM, and pH, all of which are clustered within a small 1.6-kbp DNA domain. pM, which is highly specific to adult skeletal muscle, lies in between pN and pH, which are ubiquitous but particularly active in heart and skeletal muscle. A ubiquitous enhancer, located just upstream of pH start sites, is necessary for the activity of both pH and pN in transient transfection assays. Using transgenic mice, we studied the sequence controlling the muscle-specific promoter pM and the relations between the three promoters and the ubiquitous enhancer. A 4.3-kbp fragment containing the three promoters and the ubiquitous enhancer showed an expression pattern consistent with that known in humans. In addition, while pH was active in both fast and slow skeletal muscles, pM was active only in fast muscle. pM activity was unaltered by the deletion of a 1.8-kbp region containing the ubiquitous enhancer and the pH promoter, whereas pN remained active only in fast skeletal muscle. These findings suggest that in fast skeletal muscle, a tissue-specific enhancer was acting on both pN and pM, whereas in other tissues, the ubiquitous enhancer was necessary for pN activity. Finally, a 2.6-kbp region containing the ubiquitous enhancer and only the pH promoter was sufficient to bring about high-level expression of pH in cardiac and skeletal muscle. Thus, while pH and pM function independently of each other, pN, remarkably, shares regulatory elements with each of them, depending on the tissue. Importantly, expression of the transgenes was independent of the integration site, as originally described for transgenes containing the beta-globin locus control region.

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]  
• vanWert, J. M., Panek, H. R., Wolfe, S. A., Grimes, S. R. (1998). The TE Promoter Element of the Histone H1t Gene Is Essential for Transcription in Transgenic Mouse Primary Spermatocytes. Biol. Reprod. 59: 704-710 [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]  
• 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]  
• Sabourin, J.-C., Kern, A.-S., Grégori, C., Porteu, A., Cywiner, C., Châtelet, F.ço.-P., Kahn, A., Pichard, A.-L. (1996). An Intronic Enhancer Essential for Tissue-specific Expression of the Aldolase B Transgenes. J. Biol. Chem. 271: 3469-3473 [Abstract] [Full Text]  
• Porcher, C., Picat, C., Daegelen, D., Beaumont, C., Grandchamp, B. (1995). Functional Analysis of DNase-I Hypersensitive Sites at the Mouse Porphobilinogen Deaminase Gene Locus. J. Biol. Chem. 270: 17368-17374 [Abstract] [Full Text]  
• Hallauer, P., Bradshaw, H., Hastings, K. (1993). Complex fiber-type-specific expression of fast skeletal muscle troponin I gene constructs in transgenic mice. Development 119: 691-701 [Abstract]