Muscle-specific gene expression. A comparison of cardiac and skeletal muscle transcription strategies.

E volution has provided the cardiovascular system with several strategies for the acquisition of tissue-specific phenotypes. Many contractile proteins, for example, are encoded by small multigene families whose differential expression in ventricular, atrial, smooth, fast-twitch, and slow-twitch muscle distinguishes one type of myogenic tissue from another. The diversity of other contractile proteins is generated from a more limited set of genes, or even a single gene, whose alternative protein products are generated by a multiplicity of posttranscriptional splicing events. Still other muscle-specific proteins, including both contractile proteins of the sarcomeres as well as tissue-specific enzymes such as the muscle isoform of creatine kinase (MCK) are identical in both the heart and skeletal muscle and are the products of the same gene (for reviews, see References 1 and 2). Most of this latter class of gene products, which are the focus of this review, are regulated at the transcriptional level; thus, study of the mechanisms regulating their expression provides an important opportunity to determine whether similar mechanisms regulate expression of the same gene in the heart and skeletal muscle or whether alternative transcriptional strategies are used. For example, many recent observations point to the myogenic determinant factors (MDFs)3A4 as the primary players involved in establishing and maintaining the induction of the myogenic program in skeletal muscle cells. The lack of the MDFs in the heart might be the cause of the differences observed in the patterns of expression of muscle-specific genes in the heart and in skeletal muscle cells. It remains to be explained how muscle-specific