INHIBITION OF MYOGENESIS IN MOUSE C2 CELLS BY DOUBLE-STRANDED PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES CONTAINING MEF-1 SEQUENCE

Phosphorothioate oligonucleotides containing the muscle creatinine kin ase enhancer sequence (mef-1) and a mutant of the enhancer sequence (m mef-1) were tested for their ability to block muscle differentiation i n mouse C2 cells in culture, Maximum inhibition of fusion of myoblasts was observed at 10 mu M concentration of mef-1 oligomer. No appreciab le inhibition of fusion with the mmef-1 oligomer at the same concentra tion was observed. Synthesis of myogenin, muscle creatinine kinase, an d myosin heavy chain polypeptides were reduced in mef-1 oligomer-treat ed cells. In contrast, no significant reduction in the synthesis of th ese polypeptides in mmef-1-treated cells was detected, The overall pro tein synthesis was not affected. These results suggest that muscle dif ferentiation may be disrupted by competition of the oligomer with the endogenous promoter for specific transcription factor(s).