M-TWIST IS AN INHIBITOR OF MUSCLE DIFFERENTIATION

The twist gene encodes a transcription factor containing a conserved b asic helix-loop-helix domain. During development, transcription factor s of this type are normally associated with the induction of different iation. Yet the expression pattern of the murine M-twist suggests an i nhibitory role during muscle differentiation. Following stable transfe ction of myogenic mouse cells with an M-twist expression vector, 75% o f M-twist-expressing clones were impaired in their ability to differen tiate. In contrast, only 15% of control clones were unable to differen tiate. Treatment with antisense oligonucleotides restored differentiat ion capacity in a concentration-dependent manner. Control oligonucleot ides had no effect. These experiments show that the mouse twist gene c an act as an inhibitor of muscle differentiation and that this inhibit ion is reversible. (C) 1994 Academic Press, Inc.