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© Research
Publication : The Journal of biological chemistry

Proximal sequences of the aldolase A fast muscle-specific promoter direct nerve- and activity-dependent expression in transgenic mice

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of biological chemistry - 12 Jun 1998

Spitz F, De Vasconcelos ZA, Châtelet F, Demignon J, Kahn A, Mira JC, Maire P, Daegelen D

Link to Pubmed [PMID] – 9614104

J. Biol. Chem. 1998 Jun;273(24):14975-81

Muscle activity is known to modulate the muscle fiber phenotype. Changes in muscle activity (normal or experimentally induced) lead to modifications of the expression status of several muscle-specific genes. However, the transcription regulatory elements involved in the adaptative response are mainly unknown. The aldolase A muscle-specific promoter, pM, is expressed in adult fast twitch muscle with a preferential expression in fast glycolytic-2B fibers. Its activity is induced during postnatal muscle maturation, suggesting a role of nerve and/or muscle activity. Indeed, denervation of gastrocnemius in newborn mice prevented the activation of the promoter in this muscle, despite the nerve-independent formation of 2B fibers. Although the nerve was necessary for pM onset during development, denervating the gastrocnemius in adults had only mild effects on pM activity. By contrast, a transgene including the pM proximal regulatory sequences that are sufficient to reproduce the 2B fiber-specific expression of the endogenous promoter was shown to be highly sensitive to both neonatal and adult denervation. Transgenes containing muscle-specific pM proximal promoter elements were used to delineate the regulatory elements involved in this response to innervation and changes in the contractile activity pattern. Nerve- and activity-dependent elements could be localized in the 130-base pair-long proximal promoter region of the human aldolase A gene.

http://www.ncbi.nlm.nih.gov/pubmed/9614104