Regulation of Wnt/Wg signaling pathway by chromatin organizer SATB1

Abstract

Abstract:

Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer that links higher-order chromatin architecture to gene regulation. In addition to its key role in gene regulation, it is also known to interact genetically/physically with components of multiple signaling pathways, one such pathway is the Wnt/Wg signaling pathway. Previous studies have shown that SATB1 interacts with β-catenin and competes with TCF7L2 for binding to it, thereby modulating the final outcome of Wnt signaling. However, it is still unclear whether recruitment of β-catenin is the only role of SATB1 in the Wnt/Wg pathway. Here, I present evidence that, in mammalian system, SATB1 also interacts with Dishevelled (Dvl/dsh), an upstream effector of the Wnt/Wg pathway. Mammalian SATB1 suppresses the phenotypes associated with Wnt/Wg activation in Drosophila, Further, ectopic expression of SATB1 resulted in upregulation of the Wnt/Wg pathway antagonists at transcript level. Thus, in the fly system SATB1 is a negative regulator of the Wn/Wg pathway. Therefore, regulation by SATB1 is a context-dependent phenomenon. Based on in-silico analysis, the fly protein defective proventriculus (DVE) was found to be structurally similar to SATB1, Expression of DVE in the background of DSH or ARM over-expression resulted in complete phenotypic rescue. While DVE was able to limit Wg expression in the wing imaginal disc, effects of SATB1 were inconclusive. Based on these observations, we hypothesize that DVE might be an ancestral molecule which evolved to give rise to SATB1 in the vertebrates.