STRUCTURE OF THE GENE ENCODING THE MURINE SCL PROTEIN

We have determined the molecular structure of the gene encoding the murine SCL protein (helix-loop-helix transcription factor). The gene consists of seven exons spanning approx. 20 kb. The intron/exon structure, coding region sequences and sequences present at the splice junctions were highly conserved between mouse and human. The 5' flanking sequence contains CCAAT and TATA consensus motifs with several putative binding sites for SP-1, AP-1 and GATA-1. Multiple mRNA transcripts were generated by alternate exon usage. The transcripts differed primarily in the 5' untranslated region (UTR), but potentially also encode a smaller SCL protein. Despite the high degree of conservation between species, the heptamer/nonamer signal sequences in the 5' region of the human SCL gene (the frequent site of SCL disruption in human leukemia) were poorly represented in the murine sequence. In keeping with this, structural abnormalities of murine SCL were uncommon in murine leukemias that express the SCL transcript.