Inhibition of myogenesis in mouse C2 cells by double-stranded phosphorothioate oligodeoxynucleotides containing mef-1 sequence.
Phosphorothioate oligonucleotides containing the muscle creatinine kinase enhancer sequence (mef-1) and a mutant of the enhancer sequence (mmef-1) were tested for their ability to block muscle differentiation in mouse C2 cells in culture. Maximum inhibition of fusion of myoblasts was observed at 10 microM concentration of mef-1 oligomer. No appreciable inhibition of fusion with the mmef-1 oligomer at the same concentration was observed. Synthesis of myogenin, muscle creatinine kinase, and myosin heavy chain polypeptides were reduced in mef-1 oligomer-treated cells. In contrast, no significant reduction in the synthesis of these polypeptides in mmef-1-treated cells was detected. The overall protein synthesis was not affected. These results suggest that muscle differentiation may be disrupted by competition of the oligomer with the endogenous promoter for specific transcription factor(s).
Parekh
R
R
Department of Molecular Biology and Genetics, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Bag
J
J
D000199:Actins / Q000096:biosynthesis / Q000302:isolation & purification; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003402:Creatine Kinase / Q000096:biosynthesis / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000187:drug effects*; D007527:Isoenzymes; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology*; D018008:Myogenin / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D018994:Myosin Light Chains / Q000096:biosynthesis / Q000302:isolation & purification; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D013873:Thionucleotides; D014335:Tropomyosin / Q000096:biosynthesis / Q000302:isolation & purification
D000199:Actins; D007527:Isoenzymes; C503801:Myog protein, mouse; D018008:Myogenin; D018994:Myosin Light Chains; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D014335:Tropomyosin; D008715:Methionine; D003402:Creatine Kinase; D018995:Myosin Heavy Chains