EXON INTRON STRUCTURE OF THE HUMAN AF-4 GENE, A MEMBER OF THE AF-4/LAF-4/FMR-2 GENE FAMILY CODING FOR A NUCLEAR-PROTEIN WITH STRUCTURAL ALTERATIONS IN ACUTE-LEUKEMIA/

The AF-4 gene on human chromosome 4q21 is involved in reciprocal trans locations to the ALL-1 gene on chromosome 11q23, which are associated with acute lymphoblastic leukaemias. A set of recombinant phage carryi ng genomic fragments for the coding region and flanking sequences of t he AF-4 gene were isolated. Phage inserts were assembled into four con tigs with 21 exons, and an intron phase map was produced enabling the interpretation of translocation-generated fusion proteins, The gene co ntains two alternative first exons, la and Ib, both including a transl ation initiation codon, The translocation breakpoint cluster region is flanked by exons 3 and 6 and two different polyadenylation signals we re identified. Polyclonal antisera directed against three different po rtions of the AF-4 protein were produced and used to detect a 116 kD p rotein in cellular extracts of human B-lymphoblastoid and proB cell li nes. In mitogen-stimulated human peripheral blood mononuclear cells th e AF-4 antigen was predominantly located in the nucleus. The AF-4 gene is a member of the AF-4, LAF-4 and FMR-2 gene family, The members of this family encode serine-proline-rich proteins with properties of nuc lear transcription factors. Comparison of AF-4 protein coding sequence s with the LAF-4 and FMR-2 sequences revealed five highly conserved do mains of potential functional relevance.