TRANSCRIPTION FACTOR RTEF-1 MEDIATES ALPHA(1)-ADRENERGIC REACTIVATIONOF THE FETAL GENE PROGRAM IN CARDIAC MYOCYTES

alpha(1)-Adrenergic receptor stimulation induces cardiac myocytes to h ypertrophy and reactivates many fetal genes, including beta-myosin hea vy chain (beta MyHC) and skeletal alpha-actin (SKA), by signaling thro ugh myocyte-specific CAT (M-CAT) cis elements, binding sites of the tr anscriptional enhancer factor-1 (TEF-1) family of transcription factor s. To examine functional differences between TEF-1 and related to TEF- 1 (RTEF-1) in alpha(1)-adrenergic reactivation of the fetal program, e xpression constructs were cotransfected with beta MyHC and SKA promote r/reporter constructs in neonatal rat cardiac myocytes. TEF-1 overexpr ession tended to transactivate a minimal beta MyHC promoter but signif icantly interfered with a minimal SKA promoter. In contrast, RTEF-1 tr ansactivated both the minimal beta MyHC and SKA promoters. TEF-1 and R TEF-1 also affected the alpha(1)-adrenergic response of the beta MyHC and SKA promoters differently. TEF-1 had no effect. In contrast, RTEF- 1 potentiated the alpha(1)-adrenergic responses of the SKA promoter an d of a -3.3-kb beta MyHC promoter. To determine why the promoters resp onded differently to TEF-1 and RTEF-1, promoters with mutated M-CAT el ements were tested in the same way. The beta MyHC promoter required an intact M-CAT element to respond to TEF-1 and RTEF-1, whereas the SKA promoter M-CAT was required for the TEF-1 response but not for the RTE F-1 response, suggesting that SKA promoter-specific cofactors may be i nvolved. By competition gel shift assay, the M-CAT of the minimal beta MyHC promoter had a lower affinity than that of the SKA promoter, whi ch partly explains the different responses of these promoters to TEF1. These results highlight functional differences between TEF-1 and RTEF -1 and suggest a novel function of RTEF-1 in mediating the alpha(1)-ad renergic response in hypertrophic cardiac myocytes.