Tetramerization of SATB1 is essential for regulating of gene expression

Special AT-rich sequence-binding protein 1 (SATB1) functions as a 'genome organizer' in tumorigenesis. Our previous report showed that SATB1 forms a tetramer through its N-terminal ubiquitin like domain rather than the proposed PDZ domain. In the present study, we aim to illustrate whether this oligomerization is critical to its function as a global repressor of gene expression in vivo. Luciferase and GST pull-down assays demonstrated that disrupting SATB1's tetramerization not only affects the activities of promoters but also influences the recruitment of interaction partners. Furthermore, we developed stable cell lines that overexpressed either the SATB1 tetramer or STAB1 dimer (KWN-AAA) and monitored global gene expression. Gene expression profiling revealed that over 1000 genes were significantly upregulated or downregulated upon the overexpression of SATB1 or the SATB1 (KWN-AAA) mutant. These data implied that SATB1 might regulate gene expression through its different oligomerization state. In conclusion, we inferred that the oligomerization of SATB1 is pivotal to its function of different biological processes.