The bcl-2 major breakpoint region (mbr) possesses transcriptional regulatory function

Abstract

The bcl-2 major breakpoint region (mbr), located within the 3′-UTR of the bcl-2 gene, is the site of the most common chromosomal translocation, t(14;18) (q32;q21), which occurs in follicular lymphoma. The mbr forms a triplex DNA structure under physiological conditions and the transcription factor special AT-rich sequence- binding protein 1 (SATB1) binds immediately downstream of the mbr. These observations raise the possibility that the mbr may be involved in regulation of bcl-2 gene expression. We investigated the role of the bcl-2 mbr on reporter gene activity and the relevance of SATB1 to this function in a variety of cell lines. We found that the mbr up-regulated reporter gene expression. Deletion of the 37-bp AT-rich SATB1 binding site abolished the bcl-2 mbr regulation of reporter gene expression. Overexpression of SATB1 enhanced bcl-2 mbr up-regulation of the reporter gene activity. Our data strongly demonstrated that the bcl-2 mbr possessed regulatory function that was related to SATB1.