Abstract
Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.
Highlights
Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways
These results suggest that the PDZ-like domain of human SATB1 is required for complex formation with Dishevelled (Dvl-1)
We observed that anti-Dvl antibody immunoprecipitated SATB1, indicating that Dvl-1 and SATB1 exist as part of a protein complex in vivo (Fig. 1D, Figure S1)
Summary
Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. Comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. These findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent. Alterations in SATB1 protein levels result in deregulation of various genes at a global level Many of these genes are involved in signaling pathways such as those mediated by TGF-β and Wnt/Wg16. Set of genes during thymocyte d evelopment3 These results suggest a possible cross-talk between SATB1 and the components of the Wnt/Wg signaling pathway. We further studied the effects of ectopic expression of SATB1 on Wnt/Wg signaling by employing both mammalian cell-line system and Drosophila as model systems
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