Role of myogenin in myoblast differentiation and its regulation by fibroblast growth factor.

In BC3H-1 cells, a model for studying the events that occur when myoblasts transform into myocytes, we observed that differentiation was associated with a 10-20-fold increase in both gene transcription and mRNA levels for myogenin, a member of the myc gene family. In contrast, the expression of the related protein MyoD1 was not influenced. This enhanced expression of myogenin was followed by morphological differentiation and increased expression of the nicotinic acetylcholine receptor, a muscle-specific gene product. Exposure of BC3H-1 cells to a 20-base myogenin antisense oligomer blocked morphological differentiation and resulted in nearly complete inhibition of acetylcholine receptor protein expression. To further study the relationship between muscle cell differentiation and myogenin gene expression, fibroblast growth factor (FGF), a known inhibitor of myogenic differentiation, was employed. FGF treatment inhibited myogenin gene transcription and BC3H-1 cell differentiation. These results demonstrate therefore that myogenin is an important regulator of skeletal muscle cell differentiation, and the expression of myogenin is under the control of FGF.