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 946 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 946 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 newline newline