CaMK activation during exercise is required for histone hyper‐acetylation and MEF2A binding at the MEF2 site on the Glu4 gene.

Abstract

Regular exercise protects against type II diabetes in part by increasing GLUT4 content. Previous work from our laboratory has established that GLUT4 expression is mediated by CaMK‐dependent binding of MEF2A to its cis element on the GLUT4 promoter. To further investigate how MEF2A binding to the GLUT4 gene is regulated, we injected rats with KN93 to inhibit CaMK II activation and measured; 1) MEF2A binding to, and histone H3 acetylation of, the MEF2 site on the GLUT4 gene by ChIP assay, 2) nuclear HDAC5 and GLUT4 contents by Western blot and 3) GLUT4 mRNA by RT‐PCR after exercise. Exercise increased CaMK II activity ∼50%, H3 acetylation and MEF2A binding to DNA ∼2‐fold and GLUT4 expression significantly. All the above increases by exercise were attenuated by KN93. Our data show that CaMK II activity modulates chromatin structure to increase MEF2A binding to the GLUT4 gene during exercise and suggests that drugs that mimic these effects might be worthy targets for controlling diabetes.