Transcriptional regulation of the type I myosin heavy chain promoter in inactive rat soleus.
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 alpha-actin promoter, were significantly reduced in the SI soleus, except activity of the -171-bp promoter, which increased. Mutation of the betae3 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 betae3 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 betae3 element are likely involved in this response.
Huey
K A
KA
Department of Physiology and Biophysics, University of California-Irvine, Irvine, CA 92697, USA.
Roy
R R
RR
Haddad
Fadia
F
Edgerton
V R
VR
Baldwin
Kenneth M
KM
D000818:Animals; D001835:Body Weight; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D020033:Protein Isoforms; D018995:Myosin Heavy Chains