Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo
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Date
2006
Journal Title
Journal ISSN
Volume Title
Publisher
Am J Physiol Endocrinol Metab 292
Abstract
Exercise and CaMK activation both increase the binding of MEF2A to
the Glut4 promoter in skeletal muscle in vivo. Am J Physiol Endocrinol
Metab 292: E413–E420, 2007. First published September 19,
2006; doi:10.1152/ajpendo.00142.2006.—In vitro binding assays
have indicated that the exercise-induced increase in muscle GLUT4 is
preceded by increased binding of myocyte enhancer factor 2A
(MEF2A) to its cis-element on the Glut4 promoter. Because in vivo
binding conditions are often not adequately recreated in vitro, we
measured the amount of MEF2A that was bound to the Glut4 promoter
in rat triceps after an acute swimming exercise in vivo, using
chromatin immunoprecipitation (ChIP) assays. Bound MEF2A was
undetectable in nonexercised controls or at 24 h postexercise but was
significantly elevated 6 h postexercise. Interestingly, the increase in
bound MEF2A was preceded by an increase in autonomous activity of
calcium/calmodulin-dependent protein kinase (CaMK) II in the same
muscle. To determine if CaMK signaling mediates MEF2A/DNA
associations in vivo, we performed ChIP assays on C2C12 myotubes
expressing constitutively active (CA) or dominant negative (DN)
CaMK IV proteins. We found that 75% more MEF2A was bound to
the Glut4 promoter in CA compared with DN CaMK IV-expressing
cells. GLUT4 protein increased 70% 24 h after exercise but was
unchanged by overexpression of CA CaMK IV in myotubes. These
results confirm that exercise increases the binding of MEF2A to the
Glut4 promoter in vivo and provides evidence that CaMK signaling is
involved in this interaction.
rats; C2C12 myotubes; chromatin immunoprecipitation assay; autonomous
calcium/calmodulin-dependent protein kinase activity; myocyte
enhancer factor 2A; glucose transporter-4
Description
Keywords
Exercise and CaMK activation
Citation
Smith, J. A., Collins, M., Grobler, L. A., Magee, C. J., & Ojuka, E. O. (2007). Exercise and CaMK activation both increase the binding of MEF2A to the Glut4 promoter in skeletal muscle in vivo. American Journal of Physiology-Endocrinology and Metabolism, 292(2), E413-E420.