Novel human TEF-1 isoforms exhibit altered DNA binding and functional properties

The transcriptional enhancer factor-1 (TEF-1) is a member of the TEA/ATTS d omain family. TEF-1 binds to GT-IIC (GGAATG), SphI (AGTATG), SphII (AGCATG) , and M-CAT (GGTATG) response elements and is involved in the transactivati on of a variety of genes, including the SV40 large T antigen, mammalian mus cle-specific genes, and human chorionic somatomammotropin genes. Also, TEF- 1 acts as a transcriptional repressor in placental cells, possibly through interaction with the TATA binding protein (TBP), preventing TBP binding to the TATA box. Here we describe the cloning, tissue-specific expression patt ern, and functional characterization of two novel TEF-1 isoforms, TEF-1 bet a and TEF-1 gamma. These isoforms most likely arise from alternative splici ng of mRNA transcribed from a single gene and involve substitutions and/or insertions in a region immediately following the DNA binding domain. TEF-1 beta appears to be widely distributed like the prototypic TEF-1, designated TEF-1 alpha, whereas TEF-1 gamma exhibits a narrower tissue-specific expre ssion pattern that includes pancreas, kidney, and skeletal and heart muscle . The relatively limited sequence alterations among these isoforms cause si gnificant changes in their DNA binding and transcriptional activities. TEF- 1 beta and TEF-1 gamma bind to GT-IIC sequences with higher affinity and re press hCS promoter more efficiently than TEF-1 alpha, These results suggest that each TEF-1 isoform may play unique regulatory roles in various tissue s.