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) join ing of the exons VIII and IX to an internal exon X splice acceptor sit e resulting in a new open reading frame (ORF) of 99 amino acids derive d from exon X sequences, (ii) the identification of an additional func tional splice acceptor site within exon X, and (iii) a new 81-nucleoti de insertion between exon VIII and exon X sequences in a novel transcr ipt form. Genomic cloning and sequence analysis of this transcribed se gment of 81 basepairs revealed that it was bordered by canonical splic e consensus sites and located in a distance of some 400 bp from both t he exons IX and X. It was therefore termed exon IXA. Novel ORFs were g enerated as a consequence of these alternative splice mechanisms resul ting in TCF-1 gene products with significantly different C-terminal pe ptide sequences, which are prone to selective protein-protein interact ions or transactivating functions.