BCL-6, A POZ ZINC-FINGER PROTEIN, IS A SEQUENCE-SPECIFIC TRANSCRIPTIONAL REPRESSOR/

Approximately 40% of diffuse large cell lymphoma are associated with c hromosomal translocations that deregulate the expression of the BCL6 g ene by juxtaposing heterologous promoters to the BCL-6 coding domain. The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc- finger motifs and an N-terminal POZ domain, suggesting that it may fun ction as a transcription factor. By using a DNA sequence selected for its ability to bind recombinant BCL-6 in vitro, we show here that BCL- 6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines. In transient transfection experiments, BCL6 can repress transcription from promoters linked to its DNA target sequence and th is activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein. We demonstrate that this pa rt of the BCL6 molecule contains an autonomous transrepressor domain a nd that two noncontiguous regions, including the POZ motif, mediate ma ximum transrepressive activity. These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid developm ent and lymphomagenesis.