Localization of exercise- and denervation-responsive elements in the mouse GLUT4 gene

Nobuyo Tsunoda, Kayo Maruyama, David W. Cooke, Daniel M. Lane, Osamu Ezaki

Research output: Contribution to journalArticlepeer-review

Abstract

Exercise training increases the expression of GLUT4 in skeletal muscle. Previous studies demonstrated that the exercise-responsive element(s) of the murine GLUT4 gene are located between bases -1001 and -442 relative to the transcription start site. To further characterize the regulatory elements in the GLUT4 gene, the regulation of GLUT4 minigenes containing -701, -551, -442, or -423 bp of the 5'-flanking region was studied in transgenic mice. All minigenes studied showed significant expression in skeletal muscle and heart, including the -423 GLUT4 minigene that lacked the myocyte enhancer factor 2 (MEF2)-binding domain (-CTAAAAATAG-) located between bases -437 and -428. The -701- and -551-bp constructs were expressed in brown adipose tissues while the -442 and -423 constructs were not. In skeletal muscle, either swimming or treadmill running up-regulated GLUT4 minigene mRNA levels in -701 and -551 transgenic mice, but not in the -442 and -423 transgenic mice. Denervation of the gastrocnemius muscle by sectioning of the sciatic nerve down-regulated minigene and endogenous GLUT4 mRNAs in all -701, -551, -442, and -423 transgenic mice. These data indicate that exercise-responsive element(s) and brown adipocyte specific element(s) are located within 109 bp between bases -551 and -442 of the GLUT4 gene, but that the cis-element for denervation-induced down-regulation of the GLUT4 gene is located downstream of base -423. Finally, the MEF2 binding site between bases -437 and -428 is not necessary for expression of GLUT4 in skeletal muscles and heart; the cis-element mediating this effect is also located downstream of base -423. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)744-751
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume267
Issue number3
DOIs
StatePublished - Jan 27 2000

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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