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J Biol Chem, Vol. 273, Issue 24, 14975-14981, June 12, 1998
Proximal Sequences of the Aldolase A Fast Muscle-specific
Promoter Direct Nerve- and Activity-dependent
Expression in Transgenic Mice
François
Spitz,
Zulmar A.
De Vasconcelos§,
François
Châtelet¶,
Josiane
Demignon,
Axel
Kahn,
Jean-Claude
Mira§,
Pascal
Maire, and
Dominique
Daegelen
From the INSERM U129, Institut Cochin de Génétique
Moléculaire, Université René Descartes Paris V, 24 rue du Faubourg Saint Jacques, 75014 Paris, France, the
§ Laboratoire de Neurobiologie, URA-CNRS 1448, Université René Descartes Paris V, 45 rue des
Saints-Pères, 75006 Paris, France, and the ¶ URA CNRS 1283, Centre Hospitalo-Universitaire Saint Antoine, 27 rue de Chaligny,
75012 Paris, France
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.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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