In vivo regulation of the b-myosin heavy chain gene in soleus muscle of suspended and weight-bearing rats

Giger, Julia M., Fadia Haddad, Anqi X. Qin, and Kenneth M. Baldwin. In vivo regulation of the b-myosin heavy chain gene in soleus muscle of suspended and weightbearing rats. Am J Physiol Cell Physiol 278: C1153–C1161, 2000.—In the weight-bearing hindlimb soleus muscle of the rat, ,90% of muscle fibers express the b-myosin heavy chain (b-MHC) isoform protein. Hindlimb suspension (HS) causes the MHC isoform population to shift from b toward the fast MHC isoforms. Our aim was to establish a model to test the hypothesis that this shift in expression is transcriptionally regulated through specific cis elements of the b-MHC promoter. With the use of a direct gene transfer approach, we determined the activity of different length b-MHC promoter fragments, linked to a firefly luciferase reporter gene, in soleus muscle of control and HS rats. In weight-bearing rats, the relative luciferase activity of the longest b-promoter fragment (23500 bp) was threefold higher than the shorter promoter constructs, which suggests that an enhancer sequence is present in the upstream promoter region. After 1 wk of HS, the reporter activities of the 23500-, 2914-, and 2408-bp promoter constructs were significantly reduced (,40%), compared with the control muscles. However, using the 2215-bp construct, no differences in promoter activity were observed between HS and control muscles, which indicates that the response to HS in the rodent appears to be regulated within the 2408 and 2215 bp of the promoter.