STRUCTURE OF THE LEUKEMIA-ASSOCIATED HUMAN CBFB GENE

We have determined the structure of the human CBFB gene, which encodes the beta subunit of the heterodimeric transcription factor core bindi ng factor (CBF). This gene becomes fused to the MYH11 gene encoding sm ooth muscle myosin heavy chain by an inversion of chromosome 16 that o ccurs in the M4Eo subtype of acute myeloid leukemia. The CBFB gene con tains 6 exons and spans 50 kb. The gene is highly conserved in animal species as distant as Drosophila, and the exon boundaries are in locat ions identical to those of the murine Cbfb homologue. The CBPB promote r region has typical features of a housekeeping gene, including high G +C content, high frequency of CpG dinucleotides, and lack of canonical TATA and CCAAT boxes. This gene has a single transcriptional start si te, 345 nucleotides upstream of the beginning of the coding region. Th e human and mouse CBFB promoters show conservation of several transcri ptional regulatory sequence motifs, including binding sites for Sp1, E ts family members, and Myc, but do not contain any CBF binding sites. The 5' end of the human CBFB gene also contains a highly polymorphic, transcribed CGG repeat that is not present in the murine homologue. (C ) 1995 Academic Press, Inc.