The BCL6 gene involved in the 3q27 translocation associated with B-cell lymphomas encodes a novel Cys2-His2 zinc finger protein. We generated a fusion protein of glutathione S-transferase and zinc finger domain of BCL6 to determine recognition sequences of BCL6 with polymerase chain reaction using random oligonucleotides of 26 bases as a ligand. A consensus of 14 nucleotides consisting of (T/A)NCTTTCNAGG(A/G)AT was identified in the recognition sequences. In a gel mobility shift assay, the probe containing the 14-nucleotide recognition sequence formed a complex with the fusion protein and nuclear proteins from Burkitt's cell lines overexpressing the BCL6 transcripts. The consensus sequence was protected from the digestion by nuclease in a DNase I footprinting assay. In conclusion, BCL6 may be involved in tumorigenesis by binding to the consensus sequences of the other genes. (C) 1994 Academic Press, Inc.