MUSCLE-ENRICHED TEF-1 ISOFORMS BIND M-CAT ELEMENTS FROM MUSCLE-SPECIFIC PROMOTERS AND DIFFERENTIALLY ACTIVATE TRANSCRIPTION

M-CAT elements mediate cardiac- and embryonic skeletal muscle-specific expression of the cardiac troponin T gene and a number of other cardi ac-specific genes. M-CAT binding factor was shown to be related to clo ned human TEF-1, a transcriptional regulator of the SV40 viral enhance r. Here we describe the cloning of TEF-I from chick heart and the iden tification of several novel isoforms. We show that TEF-1 mRNA is consi derably enriched in cardiac and skeletal muscle, consistent with a pro posed role in muscle gene transcription. The predominant TEF-1 isoform s, TEF-1A and a novel isoform TEF-1B, bind M-CAT elements with high af finity and in a sequence-specific manner. We further demonstrate that the C-terminal portion of TEF-1B, which contains the 13-amino acid exo n that distinguishes this isoform, can activate transcription when lin ked to a heterologous DNA binding domain, while the same domain of TEF -1A cannot. Therefore, isoforms of TEF-1 may play different roles in t he regulation of M-CAT-dependent promoters in striated muscle cells.