Reversibility of muscle differentiation in the absence of commitment: analysis of a myogenic cell line temperature-sensitive for commitment

Abstract

The interrelationship between commitment (irreversible withdrawal from the cell cycle) and muscle-specific gene expression was analyzed with the myogenic cell line ts 3b-2, which is temperature sensitive for commitment and cell fusion. The rates of synthesis and levels of accumulation of muscle-specific mRNAs and proteins in the ts 3b-2 cells at permissive and nonpermissive temperatures are comparable, indicating that neither commitment nor cell fusion is required for induction of muscle-specific gene expression. In the absence of commitment, the cells are reversibly withdrawn from the cell cycle during gene induction, and expression of the muscle-specific genes is deinduced upon the switch to growth-stimulating conditions. The deinduction reflects coordinate and preferential cessation of muscle-specific mRNA synthesis, coupled with destabilization of the muscle-specific mRNAs in the cytoplasm, without effect on constitutively expressed housekeeping protein genes. The phenotype of the ts 3b-2 cells demonstrates that commitment and muscle-specific gene expression are both required, but alone are insufficient, to produce the terminally differentiated muscle phenotype.