Transcriptional regulation of the type I myosin heavy chain promoter in inactive rat soleus

Abstract

Chronic muscle inactivity with spinal cord isolation (SI) decreases expression of slow type I myosin heavy chain (MHC) while increasing expression of the faster MHC isoforms, primarily IIx. The purpose of this study was to determine whether type I MHC downregulation in the soleus muscle of SI rats is regulated transcriptionally and to identify cis-acting elements or regions of the rat type I MHC gene promoter involved in this response. One week of SI significantly decreased in vivo activity of the −3500-, −408-, −299-, −215-, and −171-bp type I MHC promoters. The activity of all tested deletions of the type I MHC promoter, relative to the human skeletal α-actin promoter, were significantly reduced in the SI soleus, except activity of the −171-bp promoter, which increased. Mutation of the βe3 element (−214/−190 bp) in the −215- and −408-bp promoters and deletion of this element (−171-bp promoter) attenuated type I downregulation with SI. Gel mobility shift assays demonstrated a decrease in transcription enhancer factor-1 binding to the βe3 element with SI, despite an increase in total binding to this region. These results demonstrate that type I MHC downregulation with SI is transcriptionally regulated and suggest that interactions between transcription enhancer factor-1 and the βe3 element are likely involved in this response.