Novel Human TEF-1 Isoforms Exhibit Altered DNA Binding and Functional Properties

• Published in: Biochemistry (Easton) 2000-03, Vol.39 (12), p.3505-3513
• Main Authors: Jiang, Shi-Wen, Trujillo, Miguel A, Sakagashira, Michiko, Wilke, Russell A, Eberhardt, Norman L
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Chickens; Cloning, Molecular; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Humans; Molecular Sequence Data; Nuclear Proteins; Protein Binding - genetics; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Isoforms - physiology; Repressor Proteins - metabolism; Repressor Proteins - physiology; TEF-1 protein; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; transcriptional enhancer factor 1; Transfection; Tumor Cells, Cultured
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi991048w

The transcriptional enhancer factor-1 (TEF-1) is a member of the TEA/ATTS domain family. TEF-1 binds to GT-IIC (GGAATG), SphI (AGTATG), SphII (AGCATG), and M-CAT (GGTATG) response elements and is involved in the transactivation of a variety of genes, including the SV40 large T antigen, mammalian muscle-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 pattern, and functional characterization of two novel TEF-1 isoforms, TEF-1β and TEF-1γ. These isoforms most likely arise from alternative splicing of mRNA transcribed from a single gene and involve substitutions and/or insertions in a region immediately following the DNA binding domain. TEF-1β appears to be widely distributed like the prototypic TEF-1, designated TEF-1α, whereas TEF-1γ exhibits a narrower tissue-specific expression pattern that includes pancreas, kidney, and skeletal and heart muscle. The relatively limited sequence alterations among these isoforms cause significant changes in their DNA binding and transcriptional activities. TEF-1β and TEF-1γ bind to GT-IIC sequences with higher affinity and repress hCS promoter more efficiently than TEF-1α. These results suggest that each TEF-1 isoform may play unique regulatory roles in various tissues.