BAZF, A NOVEL BCL6 HOMOLOG, FUNCTIONS AS A TRANSCRIPTIONAL REPRESSOR

The BCL6 gene, which has been identified from the chromosomal transloc ation breakpoint in B-cell lymphomas, functions as a sequence-specific transcriptional repressor. We cloned a novel Bcl6-homologous gene, BA ZF (encoding Bcl6-associated zinc finger protein). The predicted amino acid sequence of BAZF indicated that the BTB/POZ domain and the five repeats of the Kruppel-like zinc finger motif are located in the NH, t erminal region and the COOH-terminal region, respectively. BAZF associ ated with Bcl6 at the BTB/POZ domain and localized in the nucleus. Sin ce zinc finger motifs of BAZF were 94% identical to those of Bcl6 at t he amino acid level, BAZF bound specifically to the DNA-binding sequen ce of Bcl6 and functioned as a transcriptional repressor. The represso r activity was associated with both the BTB/POZ domain and the middle portion of BAZF. The 17-amino-acid sequence in the middle portion was completely conserved between BAZF and Bcl6, and the conserved region w as critical for the repressor activity. Expression of BAZF mRNA, like that of Bcl6 mRNA, was induced in activated lymphocytes as an immediat e-early gene. Therefore, the biochemical character of BAZF is similar to that of Bcl6 although the tissue expression pattern of BAZF differs from that of Bcl6. This is apparently the first report of a gene fami ly whose members encode zinc finger proteins with the BTB/POZ domain.