The t(14,18) chromosomal translocation that occurs in human follicular lymphoma 
constitutively activates the BCL2 gene and disrupts control of apoptosis. 
Interestingly, 70% of the t(14,18) translocations are confined to three 15-bp 
clusters positioned within a 150-bp region (major breakpoint region or [MBR]) in 
the untranslated portion of terminal exon 3. We analyzed DNA-protein 
interactions in the MBR, as these may play some role in targeting the 
translocation to this region. An 87-bp segment (87MBR) immediately 3' to 
breakpoint cluster 3 was essential for DNA-protein interaction monitored with 
mobility shift assays. We further delineated a core binding region within 87MBR: 
a 33-bp, very AT-rich sequence highly conserved between the human and mouse BCL2 
gene (37MBR). We have purified and identified one of the core factors as the 
matrix attachment region (MAR) binding protein, SATB1, which is known to bind to 
AT-rich sequences with a high propensity to unwind. Additional factors in 
nuclear extracts, which we have not yet characterized further, increased SATB1 
affinity for the 37MBR target four- to fivefold. Specific binding activity 
within 37MBR displayed cell cycle regulation in Jurkat T cells, while levels of 
SATB1 remained constant throughout the cell cycle. Finally, we demonstrated in 
vivo binding of SATB1 to the MBR, strongly suggesting the BCL2 major breakpoint 
region is a MAR. We discuss the potential consequences of our observations for 
both MBR fragility and regulatory function.