THE DNA-BINDING DOMAIN OF THE A-MYB TRANSCRIPTION FACTOR IS RESPONSIBLE FOR ITS B-CELL-SPECIFIC ACTIVITY AND BINDS TO A B-CELL 110-KDA NUCLEAR-PROTEIN

Expression studies as well as the use of transgenic animals have demon strated that the A-MYB transcription factor plays central and specific role in the regulation of mature B cell proliferation and/or differen tiation, Furthermore, it is highly expressed in Burkitt's lymphoma cel ls and may participate in the pathogenesis of this disease, We have th erefore investigated the transcriptional activity of A-MYB and its reg ulation in several human lymphoid cell lines using co-transfection ass ays and show that A-MYB is transcriptionally active in all the B cell lines studied, but not in T cells. In particular the best responder ce ll line was the Burkitt's cell line Namalwa. The activity of A-MYB in B and not T cells was observed when either an artificial construct or the c-MYC promoter was used as a reporter. Furthermore, the functional domains responsible for DNA binding, transactivation, and negative re gulation, previously characterized in a fibroblast context, were found to have similar activity in B cells, The region of A-MYB responsible for the B cell specific activity was defined to be the N-terminal 218 amino acids containing the DNA binding domain. Finally, a 110-kDa prot ein has been identified in the nuclei of all the B, but not T, cell li nes that specifically binds to this A-MYB N-terminal domain, We hypoth esize that this 110-kDa protein may be a functionally important B cell -specific co-activator of A-MYB.