THE HUMAN HIGH-MOBILITY GROUP (HMG)-BOX TRANSCRIPTION FACTOR TCF-1 - NOVEL ISOFORMS DUE TO ALTERNATIVE SPLICING AND USAGE OF A NEW EXON IXA

The C-terminal peptide sequences of the human lymphocyte-specific high mobility group (HMG)-box transcription factor TCF-1 are determined by alternative splice mechanisms affecting the exons VIII to X. Here we report, in addition to four splice forms described previously (TCF-1A, B, C,D), the identification of three novel transcripts designated TCF-1E, F, G. Cloning and sequencing of the novel cDNAs revealed (i) joining of the exons VIII and IX to an internal exon X splice acceptor site resulting in a new open reading frame (ORF) of 99 amino acids derived from exon X sequences, (ii) the identification of an additional functional splice acceptor site within exon X, and (iii) a new 81-nucleotide insertion between exon VIII and exon X sequences in a novel transcript form. Genomic cloning and sequence analysis of this transcribed segment of 81 basepairs revealed that it was bordered by canonical splice consensus sites and located in a distance of some 400 bp from both the exons IX and X. It was therefore termed exon IXA. Novel ORFs were generated as a consequence of these alternative splice mechanisms resulting in TCF-1 gene products with significantly different C-terminal peptide sequences, which are prone to selective protein-protein interactions or transactivating functions.