Activation of a muscle-specific enhancer by the Ski proto-oncogene.
In transgenic mice, muscle-specific expression of the c-ski oncogene induces hypertrophy exclusively in a subset of fast muscle fibers. Here we report that regulatory elements from two genes expressed in fast fibers, myosin light chain 1/3 (MLC) and muscle creatine kinase (MCK), were activated when co-transfected with c-ski expression vectors in myoblasts. The expression from the MLC enhancer was reduced when the c-ski oncogene was cotransfected with MyoD into NIH3T3 fibroblasts. Activation of the MLC enhancer by Ski also occurred in vivo, since bigenic progeny generated by mating MLC-CAT and MSV-skitransgenic mice displayed higher CAT activity in their muscles than did the MLC-CAT parental line. Identification of gene targets for the fiber-specific action of the c-ski gene product provides a molecular model that could be used for the further dissection of Ski-induced hypertrophy, both in tissue culture and in vivo.
Engert
J C
JC
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Servaes
S
S
Sutrave
P
P
Hughes
S H
SH
Rosenthal
N
N
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003402:Creatine Kinase / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics; D009218:Myosins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D009053:Sarcoma Viruses, Murine / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D017570:MyoD Protein; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C512653:Ski protein, mouse; D015500:Chloramphenicol O-Acetyltransferase; D003402:Creatine Kinase; D009218:Myosins