PEBP2-ALPHA-B MOUSE AML1 CONSISTS OF MULTIPLE ISOFORMS THAT POSSESS DIFFERENTIAL TRANSACTIVATION POTENTIALS/

A murine transcription factor, PEBP2, is composed of two subunits, alp ha and beta. There are two genes in the mouse genome, PEBP2 alpha A an d PEBP2 alpha B, which encode the alpha subunit. Two types of the alph a B cDNA clones, alpha B1 and alpha B2, were isolated from mouse fibro blasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously desc ribed alpha B protein referred to as alpha B1, while the 7.9-kb RNA en codes a 387 amino-acid protein, termed alpha B2, which is identical to alpha B1 except that it has an internal deletion of 64 amino acid res idues. Both alpha B1 and alpha B2 associate with PEBP2 beta and form a heterodimer. The alpha B2/beta complex binds to the PEBP2 binding sit e two- to threefold more strongly than the alpha B1/beta complex does. alpha B1 stimulates transcription through the PEBP2 site about 40-fol d, while alpha B2 is only about 25 to 35% as active as alpha B1. Trans activation domain is located downstream of the 128-amino-acid runt hom ology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that alpha A, alpha B, and beta genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are synten ic with the human AML1 on chromosome 21q22 and PEBP2 beta/CBF beta on 16q22 detected at the breakpoints of characteristic chromosome translo cations of the two different subtypes of acute myeloid leukemia. These results suggest that the previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respect ively, lack the transactivation domain of AML1.