Identification of negative regulatory regions within the first exon and intron of the BCL6 gene

Chromosomal translocations involving BCL6 gene are frequent in human B-cell lymphomas, Chromosomal breaks preferentially occur within a 3-kb region co ntaining the first exon and intron, Recent reports have revealed that inter nal deletions or point mutations also are common in this region, suggesting that structural alteration of this region may be a crucial event in the de velopment of lymphomas, In this study, we identified two regions in the BCL 6 gene that negatively regulate BCL6 expression, One region, ES, is located within the first exon between nucleotides +472 and +543, and a second regi on, IS, is located between +783 and +918 of the first intron, A consensus n ucleotide sequence for the binding of the BCL6 protein itself was found wit hin the ES region. An electrophoretic mobility shift assay and a co-transfe ction experiment using a BCL6 expression vector showed that transcription o f the BCL6 gene was negatively regulated by the BCL6 gene product. The IS r egion which is included in the regions commonly deleted in B-cell lymphomas had a silencer activity. Structural alterations of these two regions may p lay roles in the deregulated expression of the BCL6 gene in B-cell lymphoma s.