M-CAT, CARG, AND SP1 ELEMENTS ARE REQUIRED FOR ALPHA(1)-ADRENERGIC INDUCTION OF THE SKELETAL ALPHA-ACTIN PROMOTER DURING CARDIAC MYOCYTE HYPERTROPHY - TRANSCRIPTIONAL ENHANCER FACTOR-I AND PROTEIN-KINASE-C AS CONSERVED TRANSDUCERS OF THE FETAL PROGRAM IN CARDIAC GROWTH

Induction of the fetal isogenes skeletal alpha-actin (skACT) and beta-myosin heavy chain (beta-MHC) is characteristic of cardiac growth in many models, suggesting a conserved signaling pathway. However, divergent regulation has also been observed. beta-Protein kinase C (PKC) and transcriptional enhancer factor-1 (TEF-1) are involved in induction of beta-MHC in alpha(1)-adrenergic stimulated hypertrophy of cultured cardiac myocytes (Kariya, K., Farrance, I. K. G., and Simpson, P. C. (1993) J. Biol. Chem. 268, 26658-26662; Kariya, K., Karns, L. R., and Simpson, P. C. (1994) J. Biol. Chem. 269, 3775-3782). In the present study, we asked whether the skACT promoter used the same mechanism. A mouse skACT promoter fragment (-113/-46) was induced by both alpha(1)-adrenergic stimulation and co-transfection of activated beta-PKC, and contained three required DNA sequence elements: M-CAT, CArG, and Sp1. The skACT M-CAT element bound TEF-1 in cardiac myocytes. Thus the skACT and beta-MHC promoters both require a TEF-1 binding site for activation by alpha(1)-adrenerse stimulation, but differ in that skACT also requires a CArG box. These results provide a potential molecular basis for divergent regulation of the fetal program, and also imply that PKC and TEF-1 are conserved transducers for this program during cardiac growth.