Ataxin-1 occupies the promoter region of E-cadherin in vivo and activates CtBP2-repressed promoter

Abstract

Ataxin-1 is a polyglutamine protein of unknown function that is encoded by the ATXN1 gene in humans. To gain insight into the function of ataxin-1, we sought to identify proteins that interact with ataxin-1 through yeast two-hybrid screening. In this study, transcriptional corepressor CtBP2 was identified as a protein that interacted with ataxin-1. CtBP2 and ataxin-1 colocalized in the nucleus of mammalian cells. Since the E-cadherin promoter is a target of CtBP-mediated repression, the relationship between ataxin-1 and the E-cadherin promoter was investigated. Chromatin immunoprecipitation assays showed that CtBP2 and ataxin-1 were recruited to the E-cadherin promoter in mammalian cells. Luciferase assays using E-cadherin promoter reporter constructs revealed that the luciferase activity was enhanced as the level of ataxin-1 protein expression increased. CtBP2 overexpression decreased E-cadherin expression, but expression of ataxin-1 inversely increased the mRNA and protein levels of endogenous E-cadherin. Interestingly, siRNA experiments showed that the transcriptional activation of ataxin-1 was associated with the presence of CtBP2. This study demonstrates that ataxin-1 occupies the promoter region of E-cadherin in vivo and that ataxin-1 activates the promoter in a CtBP2-mediated transcriptional regulation manner. (C) 2011 Elsevier B.V. All rights reserved.