Transactivation of the human c-myc gene by c-Myb

We analyse the contribution of six Myb-binding sites in the upstream c-myc sequences to transactivation by co-transfection assays. Surprisingly, deletion of the six Myb-binding sites did not influence the transactivation of c-myc by c-Myb protein. Instead, the strongest transactivation was observed with a c-myc reporter plasmid which contains only 450 bp of exon 1 including the c-myc promoter P2. An exchange of the DNA binding domain of c-Myb by that of GAL4 led only to small transactivation effects indicating that the DNA binding domain of c-Myb is essential for transactivation of the c-myc gene. These results suggest either an indirect transactivation mechanism of the c-myc gene by c-Myb proteins or a role of the DNA binding domain for additional effects than DNA binding.