INTRINSIC TRANSCRIPTIONAL ACTIVATION-INHIBITION DOMAINS OF THE POLYOMAVIRUS ENHANCER-BINDING PROTEIN-2 CORE BINDING-FACTOR ALPHA-SUBUNIT REVEALED IN THE PRESENCE OF THE BETA-SUBUNIT

A member of the polyomavirus enhancer binding protein 2/core binding f actor (PEBP2/CBF) is composed of PEBP2 alpha B1/AML1 (as the alpha sub unit) and a beta subunit. It plays an essential role in definitive hem atopoiesis and is frequently involved in the chromosomal abnormalities associated with leukemia. In the present study, we report functionall y separable modular structures in PEBP2 alpha B1 for DNA binding and f or transcriptional activation. DNA binding through the Runt domain of PEBP2 alpha B1 was hindered by the adjacent carboxyterminal region, an d this inhibition was relieved by interaction with the beta subunit. U tilizing a reporter assay system in which both the alpha and beta subu nits are required to achieve strong transactivation, we uncovered the presence of transcriptional activation and inhibitory domains in PEBP2 alpha B1 that were only apparent in the presence of the beta subunit. The inhibitory domain keeps the full transactivation potential of ful l-length PEBP2 alpha B1 below its maximum potential. Fusion of the tra nsactivation domain of PEBP2 alpha B1 to the yeast GAL4 DNA-binding do main conferred transactivation potential, but further addition of the inhibitory domain diminished the activity. These results suggest that the activity of the alpha subunit as a transcriptional activator is re gulated intramolecularly as well as by the beta subunit. PEBP2 alpha B 1 and the beta subunit were targeted to the nuclear matrix via signals distinct from the nuclear localization signal. Moreover, the transact ivation domain by itself was capable of associating with the nuclear m atrix, which implies the existence of a relationship between transacti vation and nuclear matrix attachment.