COORDINATE REGULATION OF MESSENGER-RNAS FROM MULTIPLE CALMODULIN GENES DURING MYOBLAST DIFFERENTIATION INVITRO

Multiple genes encoding identical calmodulin molecules have been found in all mammalian species so far examined, but little is known regarding the factors involved in regulating the expression of this gene family. We have investigated the possibility of differential regulation under conditions of cell cycle withdrawal and differentiation in the nonfusing BC3H1 myoblast. Transcripts from the three genes are expressed in myoblasts and myocytes and each of the mRNA species decreases during BC3H1 differentiation. Calmodulin protein levels also decrease, although with distinct kinetics with respect to the mRNAs. Previous studies indicated that a decrease in transcription is involved (Epstein et al., Molecular Endocrinology 3:193-202, 1989). In this study, an increase in stability for each of the mRNA species is also shown to contribute to overall mRNA levels. The calmodulin mRNAs are also found to decrease under conditions of cell cycle withdrawal when differentiation is blocked. This demonstrates that the expression of mRNA from all three genes is directly coupled with the proliferation state but only indirectly with the differentiation state. Consistent with this, calmodulin expression decreases in serum deprived fibroblasts as they exit the cell cycle.