PEBP2αB/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials

A murine transcription factor, PEBP2, is composed of two subunits, α and β. There are two genes in the mouse genome, PEBP2αA and PEBP2αB, which encode the α subunit. Two types of the αB cDNA clones, αB1 and αB2, were isolated from mouse fibroblasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously described αB protein referred to as αB1, while the 7.9-kb RNA encodes a 387-amino-acid protein, termed αB2, which is identical to αB1 except that it has an internal deletion of 64 amino acid residues. Both αB1 and αB2 associate with PEBP2β and form a heterodimer. The αB2/β complex binds to the PEBP2 binding site two- to threefold more strongly than the αB1/β complex does. αB1 stimulates transcription through the PEBP2 site about 40-fold, while αB2 is only about 25 to 45% as active as αB1. Transactivation domain is located downstream of the 128-amino-acid runt homology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that αA, αB, and β genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are syntenic with the human AML1 on chromosome 21q22 and PEBP2β/CBFβ on 16q22 detected at the breakpoints of characteristic chromosome translocations 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), respectively, lack the transactivation domain of AML1.