SATB1 is expressed primarily in thymocytes and orchestrates temporal and spatial 
expression of a large number of genes in the T-cell lineage. SATB1 binds to the 
bases of chromatin loop domains in vivo, recognizing a special DNA context with 
strong base-unpairing propensity. The majority of thymocytes are eliminated by 
apoptosis due to selection processes in the thymus. We investigated the fate of 
SATB1 during thymocyte and T-cell apoptosis. Here we show that SATB1 is 
specifically cleaved by a caspase 6-like protease at amino acid position 254 to 
produce a 65-kDa major fragment containing both a base-unpairing region 
(BUR)-binding domain and a homeodomain. We found that this cleavage separates 
the DNA-binding domains from amino acids 90 to 204, a region which we show to be 
a dimerization domain. The resulting SATB1 monomer loses its BUR-binding 
activity, despite containing both its DNA-binding domains, and rapidly 
dissociates from chromatin in vivo. We found this dimerization region to have 
sequence similarity to PDZ domains, which have been previously shown to be 
involved in signaling by conferring protein-protein interactions. SATB1 cleavage 
during Jurkat T-cell apoptosis induced by an anti-Fas antibody occurs 
concomitantly with the high-molecular-weight fragmentation of chromatin of 
~50-kb fragments. Our results suggest that mechanisms of nuclear degradation 
early in apoptotic T cells involve efficient removal of SATB1 by disrupting its 
dimerization and cleavage of genomic DNA into loop domains to ensure rapid and 
efficient disassembly of higher-order chromatin structure.