The special AT-rich DNA-binding protein 1 (SATB1) is a matrix attachment region 
(MAR)-binding protein that acts as a global repressor via recruitment of 
CtBP1:HDAC1-containing co-repressors to its binding targets. The N-terminal 
PSD95/Dlg-A/ZO-1 (PDZ)-like domain of SATB1 mediates interactions with several 
chromatin proteins. In the present study, we set out to address whether the 
PDZ-domain-mediated interactions of SATB1 are critical for its in vivo function 
as a global repressor. We reasoned that since the N-terminal PDZ-like domain 
(amino acid residues 1-204) lacks DNA binding activity, it would fail to recruit 
the interacting partners of SATB1 to its genomic binding sites and hence would 
not repress the SATB1-regulated genes. Indeed, in vivo MAR-linked luciferase 
reporter assay revealed that overexpression of the PDZ-like domain resulted in 
de-repression, indicating that the PDZ-like domain exerts a dominant negative 
effect on genes regulated by SATB1. Next, we developed a stable dominant 
negative model in human embryonic kidney (HEK) 293T cells that conditionally 
expressed the N-terminal 1-204 region harbouring the PDZ-like domain of SATB1. 
To monitor the effect of sequestration of the interaction partners on the global 
gene regulation by SATB1, transcripts from the induced and uninduced clones were 
subjected to gene expression profiling. Clustering of expression data revealed 
that 600 out of 19000 genes analysed were significantly upregulated upon 
overexpression of the PDZ-like domain. Induced genes were found to be involved 
in important signalling cascades and cellular functions. These studies clearly 
demonstrated the role of PDZ domain of SATB1 in global gene regulation 
presumably through its interaction with other cellular proteins.