title: Proximal sequences of the aldolase A fast muscle-specific promoter direct nerve- and activity-dependent expression in transgenic mice.
abstract: 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.
authors.affiliation: INSERM U129, Institut Cochin de Génétique Moléculaire, Université René Descartes Paris V, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Spitz
authors.forename: Z A
authors.initials: ZA
authors.lastname: De Vasconcelos
authors.forename: F
authors.initials: F
authors.lastname: Châtelet
authors.forename: J
authors.initials: J
authors.lastname: Demignon
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: J C
authors.initials: JC
authors.lastname: Mira
authors.forename: P
authors.initials: P
authors.lastname: Maire
authors.forename: D
authors.initials: D
authors.lastname: Daegelen
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D009121:Muscle Denervation / Q000009:adverse effects / Q000379:methods; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000294:innervation*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D005634:Fructose-Bisphosphate Aldolase