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

Soyeon Lee, Sunghoi Hong, Sungsu Kim, Seongman Kang

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Original languageEnglish
Pages (from-to)713-722
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1813
Issue number5
DOIs
Publication statusPublished - 2011 May

Keywords

  • Activation
  • Ataxin-1
  • CtBP2
  • E-cadherin
  • Repression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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