GENOMIC ORGANIZATION AND ISOFORMS OF THE MOUSE ELP GENE

Analysis was made on the genomic structure, functions, and expression of the mouse ELF gene, which codes for the embryonal long terminal rep eat binding protein, Extensive screening of the cDNA library of embryo nal carcinoma cells (EC cells) identified four isoforms of ELF: ELP1 ( the original ELF isolate), ELP2, ELP3, and Ad4BP/SF1. Analysis of the genomic sequences revealed that these ELF isoforms were generated by a lternative promoter usage and differential splicing. The mRNAs of isof orms initiated at four transcription start sites distributed on three exons, Sequence analysis of the four isoforms identified three polypep tides. The N-terminal portion of ELP1 and ELP2 was longer than ELP3, a nd Ad4BP/SF1 by 77 aa. The DNA-binding domain and region II were share d by all four isoforms. The C-terminal portion shared by ELP2, ELP3, a nd Ad4BP/SF1 was 131 aa in length, and that specific to ELP1 was 57 aa in length. The ELP3 and Ad4BP/SF1 isoforms were identical for the cod ing sequence, but the two differed at the 5' noncoding region, Region II and III domains of nuclear receptors mere thought to be involved in ligand-binding and transcriptional activation. ELP1, which lacked reg ion III, functioned as a repressor, The isoforms carrying intact regio n II and region III functioned as transactivators. Expression of the f our isoforms was studied in mouse tissues and in tissue culture cells by quantitative reverse transcriptase-polymerase chain reaction (RT-PC R) analysis. Complex patterns of expression of these isoforms were obs erved in various tissues. All four ELF isoforms were expressed only in EC cells.