Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle
McGee, Sean L., Sparling, David, Olson, Ann-Louise and Hargreaves, Mark 2006, Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle, FASEB journal, vol. 20, no. 2, pp. 348-349.
Attached Files
(Some files may be inaccessible until you login with your Deakin Research Online credentials)
Name
Description
MIMEType
Size
Downloads
Title
Exercise increases MEF2- and GEF DNA-binding activity in human skeletal muscle
Federation of American Societies for Experimental Biology
Place of publication
Bethesada, Md.
Publication date
2006-02
ISSN
0892-6638 1530-6860
Summary
Diabetes is quickly reaching epidemic proportions, with 216 million people worldwide predicted to be diagnosed with the disease by 2010. While it appears that the expression of the insulin responsive glucose transporter isoform 4 (GLUT4) is not reduced in diabetic populations, overexpression of GLUT4 exclusively in muscle enhances insulin action and improves glucose homeostasis. Consequently, understanding the regulation of GLUT4 expression is considered important in identifying potential therapeutic targets for the treatment and management of insulin resistance and related disorders such as type 2 diabetes. Using transgenic mice, we have identified two conserved regions on the GLUT4 gene promoter that are required for normal skeletal muscle GLUT4 expression. The first region contains a binding site for the myocyte enhancer factor 2 (MEF2) transcription factor, between –464 and –473 bp, and it appears that a MEF2A/D heterodimer binds this sequence. However, this site is not sufficient to support full GLUT4 expression, and another region between –712 and –742 bp, termed Domain 1, is also required. A novel transcription factor, named the GLUT4 enhancer factor (GEF), was found to bind to this region. It appears that MEF2 and GEF physically interact in order to induce GLUT4 expression. A single bout of exercise is sufficient to increase both GLUT4 transcription and mRNA abundance. However, the molecular mechanisms underpinning this response remain largely unexplored, particularly in human skeletal muscle. Therefore, the aim of this study was to determine whether a single, acute bout of exercise increases the DNA-binding activity of both MEF2 and GEF in human skeletal muscle.
Language
eng
Field of Research
060114 Systems Biology
Socio Economic Objective
970106 Expanding Knowledge in the Biological Sciences